Pathogenesis Of Dpn And

Although the exact etiology of DPN and DAN is unknown, the Diabetes Control and Complications Trial (DCCT) confirmed the long-held concept that DPN and DAN are the result of sustained hyperglycemia in type 1 patients and not insulin deficiency and or autoimmunity alone (7). The mechanisms underlying the metabolic and vascular changes that occur in complication-prone tissues in the presence of acute and chronic hyperglycemia are an active area of research. Multiple etiologies have been proposed...

Risks of Insulin Therapy

Insulin is a life-sustaining medication for patients with type 1 diabetes. However, it does have important risks of which patients must be informed. Many of these risks increase as glycemic targets approach physiologic levels and the hemoglobin A1c is near normal. The most feared complication of insulin treatment is hypoglycemia, because it can be potentially life threatening. Hypoglycemia results when too much insulin is given relative to the baseline glucose level, the carbohydrate intake,...

Glucose Homeostasis

Plasma glucose concentrations are normally maintained within a narrow range reflecting a balance between glucose production and glucose utilization. Postprandi-ally, glucose is derived from carbohydrate sources in the diet, whereas in the fasting state, glucose is released from the liver, initially through glycogenolysis and, with more prolonged fasting, through gluconeogenesis. The kidney may also contribute to overall endogenous glucose production during the postabsorptive state. The kidney...

Contents

1 Epidemiology of Type 1 Diabetes Janice S. Dorman, Ronald E. LaPorte, and Thomas J. Songer 3 Massimo Pietropaolo and Massimo 3 Prediction and Prevention of Type 1 Diabetes Aristides K. Maniatis and George S. 4 Molecular Biology of P-Cell Destruction by Autoimmune Processes Ake Lernmark and Choon Hee 5 Type 1 Diabetes in Autoimmune Syndromes Tiinamaija Tuomi and Jaakko 6 The Metabolic Basis of Insulin Secretion Nicolai M. Doliba and Franz M. 7 Prevention and Correction of Hypoglycemia Relevance...

Transforming Growth Factora and Gastrin

Transforming growth factor-a (TGF-a) is a member of the EGF family and is a lig-and for the EGF receptor, a tyrosine kinase receptor. TGF-a is synthesized as a 160-amino-acid transmembrane precursor. The 50-amino-acid mature form is generated by proteolytic cleavage of a soluble form from a membrane-bound domain. Pro-TGF-a is able to bind to EGFR on adjacent cells and is biologically active, albeit at a reduced level. TGF-a overexpression in pancreatic acinar cells of transgenic mice, under the...

Experimental Illustrations Of The Basic Model

As has been reviewed in an earlier section, stimulus secretion coupling in pancreatic P-cells stimulated by glucose and amino acids (AA) is mediated by metabolic coupling factors that are generated by energized mitochondria of the secretory cells. To assess the mechanisms by which different nutrients stimulate insulin release from pancreatic P-cells, we employed nuclear magnetic resonance (NMR) technology, respirometry and biochemical analysis to study the metabolic events that occurred in...

Sickday Rules

Children with intercurrent illnesses, such as infections or vomiting, should be closely monitored for elevations in blood glucose levels and ketonuria. On sick days, blood glucose levels should be checked every 2 h and the urine should be checked for ketones with every void. Supplemental doses of short-acting insulin (0.1-0.3 U kg) should be given every 2-4 h for elevations in glucose and ketones. Because of its more rapid absorption, lispro will lower plasma glucose faster than regular insulin...

Genetic Risk

Approximately 1 300 children in the United Sates develop type 1A diabetes throughout their life, with a reported incidence of approx 15 100,000. Finland has the highest incidence, approaching 50 100,000 (16), and Japan has one of the lowest (approx 1 100,000 in children). The incidence appears to be increasing worldwide and recent Fig. 1. Hypothetical stages in the development of type 1A diabetes. IDDM, insulin-dependent diabetes mellitus. (Modified from ref. 2.) Fig. 1. Hypothetical stages in...

Clinical Presentation Of

Diabetic polyneuropathy can be staged as subclinical (class I) and clinical (class II) (see Table 2) (93). Patients with subclinical DPN lack clinical signs or symptoms but have peripheral nerve dysfunction measured by nerve conduction studies and or quantitative sensory testing. Clinical DPN is present in patients with signs and or symptoms and abnormal nerve conduction studies and or quantitative sensory testing (see Table 2). DPN is not a single entity it encompasses several distinct...

Timing Of Delivery

When pregnancy is complicated by hyperglycemia, the risk of stillbirth increases as term approaches (58). In an attempt to decrease these losses, obstetricians have delivered such pregnancies electively between 35 and 38 wk of gestation. However, this approach may have caused significant neonatal morbidity because of prematurity and hyaline membrane disease (59). Neonatal morbidity can be markedly reduced if delivery is delayed until pulmonary maturity is documented (59). Eighty percent of...

Von Meyenburg Complex And Type 2 Diabetes

Pathologic anatomy of the pancreas in juvenile diabetes mellitus. Diabetes 1965 14 619-633. 2. von Meyenburg H. ber insulitis bei diabetes. Schweitz Med Wochenschr 1940 21 554-561. 3. Gepts W, LaCompte PM. The pancreatic islets in diabetes. Am J Med 1981 70 105-115. 4. Rahier J, Goebbels RM, Henquin JC. Cellular composition of the human diabetic pancreas. Dia-betologia 1983 24 366-371. 5. Lernmark , Kl ppel G, Stenger D, Vathanaprida C, F lt K, Landin-Olsson M, et al. Heterogeneity of...

References

Glaser N, Barnett P, McCaslin I, Nelson D, Trainor J, Louie J, et al. Risk factors for cerebral edema in children with diabetic ketoacidosis. N Engl J Med 2001 344 264-269. 2. Eisenbarth GS. Type I diabetes mellitus. A chronic autoimmune disease. N Engl J Med 1986 314 1360-1368. 3. Atkinson MA, Eisenbarth GS. Type 1 diabetes new perspectives on disease pathogenesis and treatment. Lancet 2001 358 221-229. 4. Verge CF, Gianani R, Kawasaki E, Yu L, Pietropaolo M, Jackson RA, et al. Prediction of...

Gastrointestinal Autonomic Neuropathy

The most common presenting symptom of gastrointestinal autonomic neuropathy is constipation (102). Other gastrointestinal tract problems that may present include gastric atony, gallbladder atony, and diabetic diarrhea or incontinence (102). DAN may also present as esophageal motility disorders such as dysphagia, retrosternal pain, and heartburn. Diabetic diarrhea is characterized by severe nocturnal exacerbations and may be secondary to intestinal motility abnormalities, sphincter malfunction,...

Increased Vessel Wall Protein Accumulation

The common pathophysiologic feature of diabetic microvascular disease is progressive narrowing and eventual occlusion of vascular lumina, which results in inadequate perfusion and function of the affected tissues. Early hyperglycemia-induced microvas-cular hypertension and increased vascular permeability contribute to irreversible microvessel occlusion by three processes. The first is an abnormal leakage of periodic acid-Schiff (PAS)-positive, carbohydrate-containing plasma proteins, which are...

General Principles Of Nutrient Sensing

The biochemical engineering of the pancreatic P-cells uniquely equips them to operate as the body's fuelstat. They respond to a representative sampling of small monomeric fuel molecules such as glucose or fatty acids, rather than to large polymeric macromolecules such as glycogen or triglycerides. All of the relevant nutrients are stimulators of insulin secretion inhibitory nutrient molecules do not seem to exist, although several hormones such as somatostatin or catecholamines can serve an...

Genitourinary Autonomic Neuropathy

The management of a neurogenic bladder includes regular urinations, with patients instructed to empty the bladder every 4 h even in the absence of the sensation of fullness, which may be coupled with the Crude maneuver. Other maneuvers to increase the force of bladder contraction include the parasympathetic agonist bethanechol (10-30 mg three times a day). An a1-blocker, such as doxazosin, can help sphincter. Self-catheterization may also be required. In more severe or refractory cases, an...

Subacute Effects of Hypoglycemia Cogntive Effects and Mood

Most research of the acute effects of hypoglycemia on cognitive performance has been performed in adults both with and without diabetes. A variety of neuropsycholog-ical tests have been used to assess cognition in these acute situations and there has been considerable variation among study results, depending on glucose nadir achieved and tests employed. The limitation of all of these studies is the difficulty in interpreting psychological test results. Although decrements may be demonstrated,...

Diabetic Foot Type

Developmental biology of the pancreas. Development 1995 121 1569-1580. 2. Edlund H. Pancreas how to get there from the gut Curr Opin Cell Biol 1999 11 663-668. 3. Bonner-Weir S, Baxter LA, Schuppin GT, Smith FE. A second pathway for regeneration of adult exocrine and endocrine pancreas a possible recapitulation of embryonic development. Diabetes 1993 42 1717-1720. 4. Wang RN, Kloppel G, Bouwens L. Duct to islet-cell differentiation and islet growth in the pancreas of duct-ligated...

Mitochondrial Diabetes

Patients with mitochondrial DNA mtDNA disease may have a clinical syndrome that involves mitochondrial dysfunction that is easy to identify. As an example, patients with mitochondrial encephalopathy with lactic acidosis and stroke-like episodes MELAS present in childhood with short stature and develop bilateral deafness in their teens, and then diabetes, seizures, stroke-like episodes, and an encephalopathy in their third or fourth decade 14 . Other patients have a constellation of clinical...

Keratopathy

Although infrequent, patients with diabetes can develop corneal problems. The diabetic cornea is known to have reduced corneal sensation 58 . This loss of sensation can predispose to the development of corneal abrasions or even neurotropic ulceration formation 59 . Those patients who develop ocular surface disorders may have delayed wound healing and this, coupled with the increased predisposition for infection in the diabetic patient, requires that they be followed closely. Because of the...

Fibroblast Growth Factors

The fibroblast growth factor FGF family of proteins is composed of at least 19 related peptides with actions that include mitogenesis, angiogenesis, and morphogenesis in a variety of fetal, neonatal, and adult tissues. FGF-1 also called acid FGF and FGF-2 also called basic FGF are present in normal adult human pancreas and are highly expressed in pancreatic tumors 91 . FGF-1 has been detected in a-cells and in acinar and ductal epithelial cells, and FGF-2 mRNA has been localized in a- and...

Postpartum

Maternal insulin requirements usually drop precipitously postpartum and these requirements may be decreased for 48-96 h postpartum. Insulin requirements should be recalcu lated at 0.6 U kg based on the postpartum weight and should be started when the 1-h postprandial plasma glucose value is above 150 mg dL or the fasting glucose level is greater than 100 mg dL. The postpartum caloric requirements are 25 kcal kg d, based on postpartum weight. For women who wish to breast feed, the calculation is...

Hla Complex And Mechanisms Of Susceptibility To Or Protection From

Amino acid polymorphism at position 57 the HLA-DQP-chain could influence the interaction between the class II molecule on the antigen-presenting cell, the peptide antigen, and the TCR of the helper T-cell. Consequently, this influences the control of the specificity of the immune response to foreign and or self antigens see Fig. 6 22 . However, other residues in the DQP-chain as well as the DQa-chain 124-126 also appear to be involved in the susceptibility to T1DM. As discussed earlier, genetic...

Defective Glucose Counterregulation

The autonomic nervous system mediates the counterregulatory response to hypoglycemia in the type 1 diabetic patient. This counterregulatory response to hypo-glycemia is comprised of an increase in hepatic glucose production and decreased peripheral glucose uptake. Patients with long-standing diabetes with or without auto-nomic neuropathy may not have typical autonomic warning signs of hypoglycemia, such as sweating and tachycardia. However, recent studies have not confirmed an etio-logic...

Preclinical Studies Animal Studies

The availability of BB rats and NOD mice has greatly enhanced our understanding of the possible pathogenic mechanisms involved in immune-mediated type 1 diabetes. The human immune response is, however, different from that of the rodents and pre-clinical trials may not always be applicable to humans. For example, macrophages play an essential role in initiating animal insulitis They are the first infiltrating cells and an immune intervention directed against macrophages prevent diabetes...

Prolactin Growth Hormone and Placental Lactogen

Several studies have demonstrated that prolactin PRL and growth hormone GH secreted by the pituitary and the closely related placental lactogen PL secreted by the placenta during pregnancy may play an important role in the regulation of pancreatic islet growth and function. In homologous systems, islet P-cells respond to PRL and PL via an increase in cell proliferation as well as an enhancement of P-cell function, through a lowering of the threshold for glucose-stimulated insulin secretion GSIS...

Actions of Insulin and Glucagon

The cardinal hormonal alteration that triggers the metabolic decompensation of DKA is insulin deficiency accompanied by an excess of glucagon and the stress hormones epinephrine, norepinephrine, cortisol, and growth hormone 2,3,6 . Insulin stimulates anabolic processes in liver, muscle, and adipose tissues and thereby permits glucose utilization and storage of the energy as glycogen, protein, and fat see Table 1 . Concurrent with these anabolic actions, insulin inhibits catabolic processes such...

Abnormal Endothelial Cell Function

Type One Diabetes

Early in the course of diabetes, before structural changes are evident, hyperglycemia causes abnormalities in blood flow and vascular permeability in the retina, glomerulus, peripheral nerve vasa nervorum 12,13 , and arterial endothelium 14 . The increase in blood flow and intracapillary pressure is thought to reflect hyperglycemia-induced Fig. 1. Lack of downregulation of glucose transport in cells affected by diabetic complications. A 2-deoxyglucose uptake in vascular smooth muscle cells...

Introduction

Type Diabetes

The development of type 1 diabetes is closely related to the disappearance of P-cells from the islets of Langerhans. Loss of P-cells was already documented in the beginning of the last century when patients died from diabetes prior to the discovery of insulin. As pointed out by Gepts 1 , authors also described inflammatory cells in the islets of Langerhans, but it was not until the post-insulin-discovery era that the inflammatory lesion was referred to as insulitis 2 . The rediscovery of...

Dietary Prescription and Monitoring

The goal of dietary management for the type 1 diabetic woman is to maintain nor-moglycemia 54 . Moreover, in the type 1 diabetic woman, the food and the insulin must match. The diet shown in Table 5 demonstrates a frequent small-feedings schedule designed to avoid postprandial hyperglycemia and preprandial starvation ketosis, as well as to promote an average weight gain of 12.5 kg in accord with the Committee on Maternal Nutrition 55 . In the obese type 1 diabetic woman gt 120 of ideal body...

P Michael Conn Series Editor

Androgens in Health and Disease, edited by Carrie Bagatell and William J. Bremner, 2003 Endocrine Replacement Therapy in Clinical Practice, edited by A. Wayne Meikle, 2003 Early Diagnosis of Endocrine Diseases, edited by Robert S. Bar, 2003 Type 1 Diabetes Etiology and Treatment, edited by Mark A. Sperling, 2003 Handbook of Diagnostic Endocrinology, edited by Janet E. Hall and Lynnette K. Nieman, 2003 Pediatric Endocrinology A Practical Clinical Guide, edited by Sally Radovick and Margaret H....

Info

Therapy is present in 14 of these patients 2 , and nephropathy is also reported. Young people with HNF-1a mutations are usually very sensitive to sulfonylureas and, indeed, may develop hypoglycemia on anything but the smallest doses. Treatment requirements are likely to increase as patients get older, because of the progressive deterioration in their glucose intolerance seen with HNF-1a mutations. Mutations in the glucokinase gene are the second most common cause of MODY. The glucokinase gene...

Behavioral And Psychosocial Considerations In Children With Diabetes

Illness in childhood has physical, psychological, and emotional implications for both the child and the family. The burdens of diabetes management present medical, cognitive, behavioral, and psychosocial challenges. Diabetes care requires families to learn and carry out complicated treatment regimens. Adhering to these regimens is also very difficult 35 . Along with learning these skills, parents must encourage adherence and even do the tasks when necessary. The way in which a family deals with...

Growth Puberty And Diabetes Insulin Deficiency And Resistance

Physical growth and development is a major feature distinguishing the child and adolescent from the mature adult. The major pathologic cause of impaired growth and maturation is inadequate nutritional supply to growing tissues, providing the basis of growth failure in most chronic diseases of childhood 2 . Diabetes may be considered an example of cellular malnutrition, whereby relative insulin deficiency leads to suboptimal or, frankly, inadequate nutrient supply to the tissues. Whereas, in...

Current Approaches

Clearly, every effort must be made to minimize the risk of iatrogenic hypoglycemia and eliminate the risk of severe hypoglycemia while pursuing the greatest degree of glycemic control that can be achieved safely in an individual person with diabetes. Hypoglycemia risk reduction involves 1 addressing the issue of hypoglycemia in every patient contact, 2 applying the principles of aggressive glycemic therapy, and 3 considering each of the comprehensive risk factors for hypoglycemia. In addition...

Respiratory Tract Infections

Whether diabetes constitutes an independent risk factor for an increased incidence or severity of common upper or lower respiratory tract infections is not clear. The overall incidence of community-acquired pneumonia may not be higher in patients with diabetes than in the normal host 22 . The odds ratio for death associated with diabetes was only 1.3 95 confidence interval, 1.1-1.5 in one large meta-analysis of community-acquired pneumonia 23 . However, the incidence of bacteremia, delayed...

Psychosocial Issues

Adolescence is an often untidy, poorly defined rite of passage characterized by exploratory, iconoclastic, sexual, and risk-taking behavior. Underpinning the apparent turmoil of adolescence is a fundamental paradox the need to identify self while conforming to a peer group 35,36 . This process has been described as a task of establishing a balance between intimacy and autonomy 37 . Although this paradox continues to some extent throughout adult life, it is during adolescence that it is most...

Diabetic Dermopathy

Diabetic dermopathy is characterized by hyperpigmented macules lt 1 cm and patches gt 1 cm on the extensor surfaces of the distal lower extremities i.e., the shins . Less commonly, similar lesions are found on the lateral foot and distal thigh 12 . Secondary findings include superficial white scale as well as atrophy in some patients, there may be preceding erythema. Additional names for this disorder include shin spots 13 and pigmented pretibial patches 14 . Although the exact cause of...

Emphysematous Pyelonephritis and Cystitis

Emphysematous pyelonephritis is a rare necrotizing infection of the renal parenchyma and perirenal tissue that is characterized by gas formation in the intrarenal and perirenal spaces. The most common causative bacterial pathogen causing this infection is E. coli. Hyperglycemia and ishemic necrosis of renal parenchyma as a result of microangiopathy produce an ideal substrate for growth of microrganisms. Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae ferment glucose, lactate, and...

Autoantibody ExpressionTCell Assays

Autoantibody Sensitivity And Specificity

More than 90 of children presenting with type 1A diabetes express one of three anti-islet autoantibodies autoantibodies reacting with insulin IAA , an islet enzyme termed glutamic acid decarboxylase 65 GAD65 , or a molecule of unknown function termed ICA512 or IA-2 4 . These autoantibodies are typically present years prior to the development of diabetes. A relatively simple rule relates most of our current knowledge for prediction of diabetes, namely expression of two or more of the above...

Caloric Intake

Energy intake is generally episodic, varying in carbohydrate, protein, and fat intake from meal to meal and day to day. Daily caloric or energy requirement is determined by daily energy expenditure. This is represented by the sum of calories required to meet the needs for resting metabolic rate RMR , the thermic effect of food TEF , and the thermic effect of physical activity or exercise TEE . Resting metabolic rate comprises 60-75 of daily caloric needs and is dependent on age, gender, body...

Mechanisms Of Immunity In Diabetes

Several factors affecting the immune system may increase the susceptibility to infections in patients with diabetes mellitus. white blood cell abnormalities have been demonstrated in the form of impaired adherence, chemotaxis, phagocytosis, and microbicidal function 2,3 . The intracellular killing of organisms by leukocytes is mediated by release of toxic free radicals, superoxides, and hydrogen peroxide. This phenomenon is referred to as the respiratory burst and is defective in patients with...

The Glucose Sensing System A Basic Model

How Model Diabetes Type

Blood glucose is the most effective physiological fuel stimulus of insulin secretion 3 . When the level of blood glucose increases, hormone secretion is enhanced with a characteristic dependency on the blood glucose level. A consensus minimal model delineating the manifold roles of glucose in insulin secretion by the P-cell has been developed. Those mechanisms are summarized schematically in Fig. 1, modified from a previous review 4 . Glucose stimulates insulin secretion by entry into P-cells...

Behavioral Strategies

All of these efforts are an attempt to raise the quality of standard care for people with diabetes. Since 1990 there has been a large focused effort to employ both diabetes education and behavioral strategy in order to improve outcomes. Increased follow-up care and comprehensive curricula are part of the trend. A meta-analysis by Roter 28 revealed that a combined educational behavioral focus is more effective than a single-focus intervention and that larger programs produced weaker effects. The...

Biological Significance Of The Vntr Region

A number of studies have suggested that the INS VNTR may have a biological role in the genetic regulation of insulin expression 70,157,158 . The proximity of this polymorphism to the INS transcriptional start site lt 400 bp upstream makes this an attractive hypothesis. Furthermore, an association between VNTR polymorphisms and human disease is not unprecedented. It has been suggested that the human HRAS1 gene, which encodes the H-ras protooncogene and is associated with a genetic susceptibility...

Defective Counterregulation

As described earlier, impaired hormonal responses to a decrease in blood glucose have been found to occur in adults with type 1 diabetes and manifest as either a diminished hormonal response and or an altered glucose threshold for hormone release these defects can be induced by exposure to antecedent hypoglycemia 73 and reversed by its elimination 76,77 . Defects in counterregulation have been found to occur after only one night of hypoglycemia 93 . This leads to delayed glucose recovery, which...

Secondary Prevention

Several trials have adopted the secondary prevention approach to delay or prevent the continued P-cell destruction in subjects that are currently euglycemic. In general, two separate agents are being studied in these trials nicotinamide and insulin. The rationale for using nicotinamide in intervention trials is based on animal models both the NOD mouse and the Bio-Breeding BB rat that nicotinamide prolongs remission, preserves P-cell function, and may prevent immune-mediated diabetes 79,80 ....

In How Many Ways Can the pCells Get Killed Killing by Virus

Since Yoon et al. 131 isolated coxsackie B4 virus from the pancreas of a patient with type 1 diabetes, various viruses have been studied to examine their diabetogenic potential and to what extent viruses represent an environmental factor that contributes to the disease. The viral infection seems to be able to indirectly activate autoreactive T-cells that, in turn, can generate initial pancreatic tissue damage. Damaged P-cells release previously ignored self antigens that may activate an...

Tertiary Prevention

The goal of tertiary prevention strategies is to induce a prolonged remission, allow for potential P-cell regeneration, and or preserve residual P-cell function, after the clinical onset of insulin deficiency. Trials using this approach have been largely unsuccessful. Early studies of immunosuppressive agents such as cyclosporin revealed that while administered, they prevented further loss of C-peptide secretion, resulting in improved metabolic function. Upon discontinuation, however, the...

Genetic Component

Severe diabetic retinopathy tends to run in families 20 and there is concordance among identical twins indicating that diabetic retinopathy has a genetic component. Several candidate gene or case-control studies have reported that there are genetic variations that are associated with an increased 21-25 or decreased 26 risk of diabetic retinopathy. This suggests that diabetic retinopathy is a genetically complex trait, meaning that there are genetic variations that increase susceptibility and...

Fluid and Electrolyte Losses

Dka Metabolic Pathways

Fluid and electrolyte abnormalities are virtually universal in patients with DKA, and, if unrecognized or mismanaged, contribute significantly to the morbidity and mortality of DKA 1-6 . Fluid and electrolyte losses in DKA vary so that the extent of these losses is unpredictable in any given patient. However, estimates of losses that form the basis of the initial management of DKA have been formulated see Table 2 . It is emphasized that these recommendations are only guidelines, that each...

Fatty Acids As Insulin Secretagogues

Fatty acids trigger secretion of insulin in a glucose-dependent manner 3,44 . Fatty acids serve as an important endogenous fuel of islet tissue incubated with low glucose or in the absence of glucose. The possibility has been considered that a high level of fatty acids may inhibit the glucokinase glucose sensor because acyl-CoA, the first metabolite in fatty acid catabolism, is a very potent inhibitor of this enzyme 3 . However, this inhibition is competitive with glucose and is therefore...

Bardetbiedl Syndrome

Bardet-Biedl syndrome BBS is an autosomal recessive condition characterized by rod-cone dystrophy atypical retinitis pigmentosa , postaxial polydactyly, central obesity, mental retardation, hypogonadism, and renal dysfunction. Other features, not always present, include hepatic fibrosis, diabetes mellitus, reproductive abnormalities, endocrinological disturbances, short stature, developmental delay, and speech deficits. BBS is distinguished from the much rarer Laurence-Moon syndrome, in which...

Rhinocerebral Mucormycosis

Almost 50 of cases of rhinocerebral mucormycosis occur in patients with diabetes 31 . Fungi of the Rhizopus and Mucor species are the most common etiologic agents of this clinical entity. These fungi are ubiquitous saprophytic organisms, not uncommonly infecting the immunocompromised host 32 . Ketoacidosis temporarily disrupts host defense mechanisms, thereby permitting growth of Rhizopus oryzae. Such growth is inhibited by correcting acidosis 33 . These fungi have a predilection to invade...

Self Monitoring of Blood Glucose

The most powerful monitoring tool is capillary blood glucose monitoring 46 . A small lancet pricks a patient's fingertip to obtain a small drop of blood that is placed on a testing strip. With electrochemical methods, the glucose concentration of this drop can be determined in 5 to 30 s. Patients with type 1 diabetes are encouraged to monitor blood glucose frequently. By determining glucose levels before a meal, patients can decide whether their insulin dose needs adjustment to counteract an...

Amount of Carbohydrate

Individuals with normal glucose tolerance experience a dose-related rise in postprandial blood glucose up to 60-75 g of carbohydrate consumed 4 . Consuming more carbohydrate does not increase blood glucose beyond 140 mg dL primarily because insulin secretion keeps up with entry of glucose into the blood. In type 1 diabetes, in which insulin secretion is absent or very low, the larger the dose of carbohydrate, the greater the blood glucose response. Studies in individuals with type 1 diabetes...

37zehrer Cl Gross Cr Comparison Of Quality Of Life Between Pancreas Kidney And Kidney Transplant Recipients One-year

The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993 329 977-986. 2. Rizza RA, Cryer PE, Gerich JE. Role of glucagon, catecholamines, and growth hormone in human glucose counterregulation. Effects of somatostatin and combined alpha- and beta-adrenergic blockade on plasma glucose recovery and glucose flux rates after...

Landmark Clinical Trials Addressing the Management of Diabetic Retinopathy The Diabetic Retinopathy Study

Numerous anecdotal reports throughout the 1960s suggested that photocoagulation provided some benefit in patients with PDR. To determine if this was the case and to better define the indications, side effects, long-term results, and complications of photocoagulation, a clinical trial, the Diabetic Retinopathy Study DRS , was commenced in 1971. The DRS demonstrated that scatter laser photocoagulation panretinal photocoagulation, PRP significantly reduced the risk of severe visual loss from PDR...

Scleredema

Scleredema Type

Although patients with this disorder develop induration hardening of the skin, scle-redema should not be confused with the distinctly different disease, scleroderma. The From Contemporary Endocrinology Type 1 Diabetes Etiology and Treatment Edited by M. A. Sperling Humana Press Inc., Totowa, NJ Fig. 1. Peau d'orange appearance of the upper back in a patient with scleroderma. The areas of involvement are firm to palpation. Fig. 1. Peau d'orange appearance of the upper back in a patient with...

Implantable Insulin Pumps

Insulin pumps that are totally implanted in the body and infuse insulin intravenously iv or intraperitoneally ip have been under development for some 20 yr 67-69 . However, unlike external pumps, they have yet to enter routine clinical practice, limited in large part by the relative invasiveness, cost, and occurrence of various complications. The advantages of implanted pumps include the pump being out of site and protected, the complete freedom from injection or insertion of a cannula needle,...

Asgfat I

Hyperglycemia increases hexosamine pathway flux. In this pathway, increased O-linked Glc-NAc moieties on the transcription factor Sp1 increase its transactivating function and thus increase transcription of complications-associated genes Reproduced with permission from ref. 103. glycolysis to provide substrates for reactions that require urine diphosphate UDP -N-acetylglucosamine, such as proteoglycan synthesis and the formation of O-linked glycoproteins. Inhibition of the rate-limiting...

Grading of Diabetic Retinopathy and Implications for Clinical Practice

Current treatment recommendations for diabetic retinopathy are based on the results of the DRS and the ETDRS. Provided that careful follow-up can be maintained, the ETDRS recommended that patients with mild or moderate NPDR generally do not Mild NPDR At least one microaneurysm, but not as severe as moderate NPDR. The presence of mild NPDR has a 5 risk of progression to PDR within 12 mo and a 15 risk of progression to high-risk PDR within 5 yr. Moderate NPDR Extensive intraretinal hemorrhages...

Insulin Lispro Use During Pregnancy Possible Effects on the Fetus

Diamond and Kormas first questioned the safety of using insulin lispro during pregnancy in a letter to The New England Journal of Medicine in 1997 46 . They reported on two patients who used insulin lispro during pregnancies and deliveries. One of these pregnancies was terminated at 20 wk gestation and the second pregnancy resulted in a seemingly healthy infant after elective cesarean delivery, but who subsequently died unexpectedly 3 wk later. Both infants were discovered to have congenital...

Fat Replacers

Fat replacers or substitutes derived from modified proteins or carbohydrates were introduced into the market to assist in efforts to decrease total fat intake. Although this is theoretically possible, few studies have documented a health benefit. Most have been behavioral studies identifying that total fat, saturated fat, and dietary cholesterol intake can be reduced with the use of these products 53 . However, little change in energy intake or body weight has been reported. Persons with...

SUMMARY

Nutritional management of type 1 diabetes is dictated by prioritizing interventions that yield optimal metabolic outcomes and enhanced quality of life. The USDA Food Guide Pyramid continues to be the basis for a healthy diet providing vitamins, minerals, phytonutients, and fiber. Blood glucose control is best achieved with careful attention to adequately covering carbohydrate intake with insulin, generally utilizing carbohydrate-counting techniques. Although individuals with well-controlled...

Islet Purification

Purification addresses the need to physically separate the islets from the surrounding nonendocrine acinar, vascular, ductal, and lymphoid tissue. Because there is a marked difference in density between endocrine and exocrine tissues, separation by density gradient centrifugation has evolved as the preferred method of purification. Purification is usually conducted on Eurocollins-Ficoll density gradients, in which the islets are centrifuged for a time sufficient to allow them to reach their...

Alstrom Syndrome

This syndrome was first described in 1959, when two of Alstrom's original patients died from renal failure 86 . The characteristic features of this syndrome appear to be pigmentary retinal degeneration, sensorineural hearing loss, childhood obesity, non-insulin-dependent diabetes mellitus, hyperlipidaemia, and chronic nephropathy. Features occasionally observed include acanthosis nigricans, hypogonadism, hypothyroidism, alopecia, short stature, and cardiomyopathy. A large kindred including...

Praderwilli Syndrome

Prader-Willi syndrome PWS is a complex, multisystem disorder first described in 1956 90 . It is diagnosed in about 1 in 10,000-15,000 people 91 , occurring in all sexes and races. Many of the manifestations are related to functional hypothalamic deficiency, and the clinical appearance in infancy differs markedly from that in childhood and adulthood 92 . The major features associated with PWS are decreased fetal activity, neonatal hypotonia and feeding difficulties, hyperphagia with obesity, and...

Mononeuropathies of the Extraocular Muscles

Palsies involving the third oculomotor , fourth superior oblique , and sixth abducens lateral rectus cranial nerves occur not uncommonly in diabetes. However, despite this definite association, one must always bear in mind the potential for other pathology, including possible life-threatening disease 50 . Palsies of the third and sixth nerves are more commonly the result of diabetes than fourth-nerve palsies, so the latter should never be attributed to diabetes without a thorough investigation...

Summary Of The Overall Dcct Results

The DCCT ended the controversy as to whether the degree of metabolic control of type 1 diabetes influences the development of long-term complications 14 . The DCCT was a prospective randomized trial that compared the effects of intensive treatment IT with those of conventional treatment CT on retinopathy, nephropathy, and neuropathy in subjects with type 1 diabetes. IT was aimed at producing normoglycemia preprandial blood glucose levels of 70-120 mg dL, HbA1c lt 6.0 and consisted of MDI three...

Conclusion

There are many unresolved questions regarding the etiology, sequelae, and prevention of this common acute complication of the treatment of type 1 diabetes. Definitions of good glycemic control that do not include a statement about absence of problematic hypoglycemia are incomplete and inadequate. The benefits of long-term good glycemic control cannot be gainsaid, but further progress in the application of intensified diabetes therapy needs to be made before it can be safely applied to all...

Type 1 Diabetes References

A Dictionary of Epidemiology. Oxford University Press, New York 1983. 2. World Bank. The World Bank overview. In World Development Report 1993. Oxford University Press, Oxford, 1993, pp. 1-16. 3. World Health Report 1999. 4. LaPorte RE, Tajima N, Akerblom HR, et al. Geographic differences in the risk of insulin-dependent diabetes mellitus the importance of registries. Diabetes Care 1985 8 Suppl 1 17-23. 5. Diabetes Epidemiology Research International Group DERI . Geographic patterns...

Malignant Otitis Externa Invasive Otitis Externa

This potentially life-threatening condition occurs in elderly diabetic patients and involves the external auditory canal and skull. Pseudomonas aeruginosa is the most common etiologic agent. However, it has also been described secondary to colonization of the external ear canal by Aspergillus species 28 . Presenting clinical features include ear discharge, severe pain, and hearing impairment, often in the absence of fever. Examination of the auditory canal shows edema, intense cellulitis, and...

Insulin Requirements

Women with type 1 diabetes must increase their insulin dosage to compensate for these diabetogenic forces of normal pregnancy. Table 3 shows that insulin requirements increase until wk 32, at which time they stabilize until the end of term. The exact pattern of insulin dosage requirement, however, is still controversial. Many observers have detected a decline in insulin requirement in late first trimester of diabetic pregnancies 38 . Others have shown no changes 39,40 or an increase 41-43 ....

Beneficial Effects On Glycemic Control

Symptoms And Effects Type Diabetes

As opposed to exogenous insulin-based therapy, successful pancreas transplantation reliably restores endogenous insulin secretion and uniquely maintains glucose levels in the normal range without significant hypoglycemia for many years. Many investigators have detailed the beneficial effects of pancreas transplantation on insulin secretion and carbohydrate metabolism. In a study of 96 pancreas-transplanted patients, fasting plasma glucose, hemoglobin A1c, glucose-induced insulin secretion, and...

Support Strategies

Clinical strategies aimed at improving diabetic control throughout adolescence have focused largely upon psychosocial support rather than clinical care. There is some evidence, however, that diabetic control is unlikely to improve from late childhood to late adolescence, and we have advocated that diabetic control needs to be optimal prior to the advent of adolescence 52 . Furthermore, research in our clinic has supported the notion that early adjustment to insulin-dependent diabetes mellitus...

Waxy Skin And Stiff Joints Cheiroarthropathy

In the dermatologic literature, the descriptive term waxy skin and stiff joints appears more commonly than the term cheiroarthropathy. The most common site of cutaneous involvement is the hands and, like scleredema, it can sometimes be confused with scleroderma. Clinically, the skin on the dorsal surface of the hands is waxy in appearance and somewhat taut 6 . A simple screening test is to ask the patient to bring his or her hands together with the palmar surfaces apposed as if one were about...

Clinical Features of Diabetic Retinopathy

Dot Hemorrhage Hard Exudate

Retinal hemorrhages are a common feature of diabetic retinopathy and vary in their appearance based on their location within the retina. The superficial capillary bed is located in the nerve fiber layer and hemorrhages from superficial capillaries have a flame-shaped appearance as the blood spreads between nerve fibers that run parallel to the retinal surface. Hemorrhages occurring from the deep capillary beds, where the arrangement of cells is perpendicular and more compact, tend to be...

The Process of Transition and the Eventual Transfer to Adult Care

In due course, the adolescent with diabetes who has been cared for in a pediatric environment, whether privately by a pediatric endocrinologist or in a pediatric clinic, must transfer care to an adult environment. The question of when and how will depend on a number of factors, including the perceived readiness of the young person, the availability of appropriate adult services, and the general policy of a hospital or clinic service. Most studies have suggested that from an adolescent's point...

Acquired Perforating Dermatosis

The perforating disorders are a group of cutaneous diseases that share a common phenomenon the outward elimination of dermal contents via claws formed by downgrowths of the epidermis. Clinically, actual plugs of degenerated collagen and elastin admixed with keratin are seen perforating through the epidermis to the surface of the skin. The primary systemic disease associated with perforating disorders is chronic renal failure CRF in particular, CRF resulting from diabetes mellitus. Occasionally,...

Urinary Tract Infection

Urinary tract infection UTI is commonly encountered in patients with diabetes 9 . However, studies have failed to demonstrate significant differences in epidemiological, clinical, and microbiological features of UTI in patients with or without diabetes except for a relative difficulty in eradicating infection in the former group 10 . Asymptomatic bacteruria occurs with a higher frequency one study demonstrated a 26 incidence in diabetic women compared to 6 in controls 11 . Whether this increase...

Activation of Protein Kinase C

Activation Pkc Hyperglycemia

Protein kinase Cs PKCs are a family of at least 11 isoforms, 9 of which are activated by the lipid second-messenger diacylglycerol DAG . Intracellular hyper-glycemia increases DAG content in cultured microvascular cells and in the retina and renal glomeruli of diabetic animals 79-81 . Intracellular hyperglycemia appears to increase DAG content primarily by increasing its de novo synthesis from the glycolytic intermediate glyceraldehyde-3-phosphate via reduction to glycerol-3-phosphate and...

Assessment

Monophasic Doppler Peripheral Artery

Treatment of a diabetic foot ulcer begins with assessment of neuropathy and arterial occlusive disease by history and physical examination. There may be a history suggesting generalized atherosclerosis. These patients often have coronary artery disease and cerebrovascular disease, as well as peripheral vascular disease. Many patients have a history of claudication 9 . Some have had a prior amputation. A detailed evaluation of pulses will determine the degree and location of atherosclerotic...

Orthostatic Hypotension

The first step in the management of orthostatic hypotension is the discontinuation, where possible, of long-acting hypotensive agents that may be contributing to the problem. Occasionally, the patient can be switched to a shorter-acting agent captopril, e.g. and the timing of the dose altered in order to minimize daytime orthostatic changes. Other non-neuropathic etiologies such as volume depletion, adrenal insufficiency, anemia, and hypothyroidism should be addressed. Typical initial...

Management Of Patients With Type Diabetes During Surgery

Optimal management of diabetes during surgery requires reliable, frequent blood glucose monitoring as well as timely and appropriate insulin replacement to maintain blood glucose in an acceptable range while avoiding ketoacidosis. The actual regimen adopted depends on the nature of the surgical procedure, expected duration of fasting, as well as the pre-existing insulin regimen. For example, for a patient using an MDI program who is due to undergo cataract extraction, diabetes could be managed...

Adrian Vella md Mrcp Uk and Robert A Rizza MD

Metabolic Consequences of Surgery in Type 1 Diabetes Evaluation of Patients with Type 1 Diabetes Prior to Surgery Management of Patients with Type 1 Diabetes During Surgery Management of Patients with Type 1 Diabetes During Emergency Surgery Conclusion References Advances in the treatment of type 1 diabetes T1DM have allowed people with this disease to live longer. Aggressive treatment of complications and the widespread use of renal transplantation and coronary artery bypass grafting have...

Emphysematous Cholecystitis

Emphysematous cholecystitis is a rare variant of acute cholecystitis caused by ischemia of the gallbladder wall and infection with gas-producing organisms. Approximately 35-55 of cases have underlying diabetes mellitus 52-54 . It is thought to result from acalculous cystic duct obstruction, with inflammatory edema eventually causing cystic artery occlusion. Colonization by gas-forming organisms causes coagu-lative necrosis of the mucosa, venous congestion, gangrene, and eventually, gallbladder...

Prevention of Progression at the Macroalbuminuria Stage

The development of macroalbuminuria UAE gt 200 g min is seen in stage IV of diabetic nephropathy. The GFR begins to decline at the rate of 5-10 per year after macroalbuminuria develops 16 . Patients in this stage may be very heterogenous with respect to the rate of progression of disease and compliance with therapy. The renal failure may occur in a few months in some, whereas others may have relatively normal renal function for years. Genetic factors probably play an important role in this...

Peripheral Autonomic Denervation

Peripheral autonomic denervation can have many clinical manifestations and contributes to changes to the skin texture, edema, venous prominence, callus formation, loss of nails, and sweating abnormalities of the feet. Diabetic subjects with neuropathic foot ulceration have been shown to have greater impairment of power spectral analysis of heart-rate variation than subjects with neuropathy without a history of foot ulcers, despite no differences being found for nerve conduction velocities 112 ....

Increased Intracellular AGE Formation

Dicarbonyl Age Precursors

Advanced glycation and products are found in increased amounts in extracellular structures of diabetic retinal vessels 42-44 and renal glomeruli 45-47 . These AGEs were originally thought to arise from nonenzymatic reactions between extracellular proteins and glucose. However, the rate of AGE formation from glucose is orders of magnitude slower than the rate of AGE formation from glucose-derived dicarbonyl precursors generated intracellularly, and it now seems likely that intracellular...

Increased Polyol Pathway Flux

Ros Type1 Diabetes

Aldose reductase is a cytosolic, monomelic oxidoreductase that catalyzes the NADPH-dependent reduction of a wide variety of carbonyl compounds, including glucose. Aldose reductase has a low affinity high Km for glucose, and at the normal glucose concentrations found in nondiabetics, the metabolism of glucose by this pathway constitutes a very small percentage of total glucose utilization. However, in a hyperglycemic environment, increased intracellular glucose concentration and possibly oxidant...

Urinary Tract Infections in Diabetes

A twofold to fourfold higher incidence of bacteriuria has been reported in diabetic women compared to nondiabetic women, although it is not seen in men 220-222 . As compared with nondiabetic women, diabetic women with bacteriuria are usually asymptomatic 223 . However, asymptomatic bacteriuria can be a predisposing factor for overt urinary tract infections UTIs 224 . Also, diabetes predisposes patients with UTI to more severe infections of the upper urinary tract and to various complications....

Avoidance of Nocturnal Hypoglycemia

Most of the studies investigating hypoglycemia prevention have focused on nocturnal hypoglycemia. There have been a number of studies examining the effect of dietary intervention on the prevalence of nocturnal hypoglycemia. Most of these studies have involved the manipulation of the bedtime snack with uncooked cornstarch being used to provide part of the carbohydrate load. The beneficial effects have been variable. Some studies found a decrease in the rate of nocturnal hypoglycemia, but these...

Bullous Diabeticorum

Bland bullae that lack a traumatic, inflammatory, or infectious etiology can arise spontaneously in the skin of patients with diabetes mellitus 43 . The most common location for these bullae is the distal lower extremity, although they have been described on the hands and forearms 44 the lesions can be up to 8 cm in diameter and are subepidermal or intraepidermal in location. The majority, but not all, of the patients have evidence of peripheral neuropathy 44 . In contrast to the water-like...

Historical Perspective

A renewal of interest for the transplantation of islets of Langerhans as a means to cure diabetes is currently being observed, as clinical studies are undertaken at an expanding number of transplant centers throughout the world. This accelerated activity is the result of several significant advances achieved at the turn of the millenium. The improved clinical results in terms of graft survival were highlighted by the recent report by the Edmonton group of a series of seven consecutive...

Obstacles to Success of Islet Allotransplantation

Islet grafts are exposed to a number of adverse conditions, some of which are shared with all types of transplant, and some of which are unique to the islets alone. The combined effects of these factors determines an imbalance between engrafted islet mass and metabolic demand, which explains why islet allografts do so poorly in comparison to islet autografts, on the one hand, and to whole-organ pancreatic allografts, on the other hand 26 . Poor engraftment is the first of these obstacles. The...

Comprehensive Risk Factors Interplay of Insulin Excess and Compromised Glucose Counterregulation

Iatrogenic hypoglycemia in T1DM is more appropriately viewed as the result of the interplay of relative or absolute therapeutic insulin excess the conventional risk factors and compromised glucose counterregulation. Three clinically well-documented risk factors for iatrogenic hypoglycemia in T1DM are 1 absolute insulin deficiency i.e., C-peptide negativity 7,29,30 , 2 a history of severe hypoglycemia 7,30 , and 3 aggressive glycemic therapy per se, as evidenced by lower glycemic goals or lower...

Costimulatory Blockade

The development of therapeutic strategies that would result in donor-specific tolerance, thus obviating the need for lifelong generalized immunosuppression, is the key subject for research as we move forward. The availability of such tolerizing protocols would be particularly interesting in islet transplantation, as it would allow large-scale transplantation of diabetic patients before the occurrence of complications. One strategy extensively explored is the blockade of costimulatory signals of...

Split Mixed Insulin Therapy

Studies such as the DCCT have shown that intensive insulin therapy reduces a patient's risk of developing the long-term complications of type 1 diabetes. Unfortunately, many patients are unable or unwilling to comply with the dosing regimens and frequent monitoring required for intensive therapy. For such patients, a treatment regimen using split-mixed insulin doses may be required. These regimens require two daily injections of a mixture of meal insulin with basal insulin. For many patients,...

GLPExendin

As with the PTHrP gene and those of many other neuroendocrine peptides, the glucagon gene encodes a number of active peptide hormones, including glucagon, glicentin, and the glucagonlike peptides GLPs . GLP-1 7-36 , acting through the seven transmembrane-spanning G-coupled protein GLP-1 receptor on the P-cell, has been shown to be a potent stimulator of P-cell replication in vitro 77-85 . It also stimulates the expression of the critical islet-specific transcription factor, PDX-1 80 ....