Intensive Insulin Therapy

In patients with DM1 and deficiency of endogenous insulin production, the exogenous insulin regimen will be designed to simulate as closely as possible the multiphasic profile of insulin secretory responses to meals and snacks present in normal subjects in order to enable targeted glycemic control. The term intensive insulin therapy is used to describe more complex insulin administration regimens in which basal insulin therapy is combined with bolus doses of insulin given three or more times...

Mechanisms Of Counterregulatory Responses To Hypoglycemia In

Glucose counterregulation is fundamentally altered in T1DM as individuals become absolutely insulin deficient and insulin levels no longer fall as glucose levels decrease (Fig. 2). -- Continued absorption of insulin -- Absent glucagon secretion Norepinephrine (4 or Blunted) Free Fatty Acids (FFA) (4 or Blunted) Glycerol (4 or Blunted) Figure 2 Diagrammatic outline of defective counterregulatory responses to hypoglycemia in T1DM. Hence, the first defense against hypoglycemia is lost. Within a...

Metformin Background

Metformin, an oral antihyperglycemic agent, has been used in the therapy of type 2 diabetes for over 40 years. Through mechanisms that have been incompletely defined, metformin lowers fasting glucose by 25 to 30 , primarily by reducing the excessive hepatic glu-coneogenesis that characterizes type 2 diabetes. Studies also point to the contribution of improved insulin-stimulated glucose uptake by peripheral tissues to metformin's effects on glycemic control (40). When added to insulin therapy in...

Demographic And Clinical Characteristics

Epidemiological data demonstrate that LADA accounts for 2 to 12 of all cases of diabetes 22,23 . A prospective observation on the natural history of the ICA type 2 diabetes patients in Japan found that the characteristic findings in this country of slowly progressive insulin dependent diabetes included a late-onset, a family history of type 2 diabetes, a slow progression of p-cell failure over several years with persistently positive low-titer ICA, and incomplete p-cell loss 24 . Similar...

Converting from a Conventional Insulin Therapy Regimen to an MDI Regimen

It is generally advisable to reduce the total daily basal insulin dose units when long-acting basal insulin is to be started at the time of conversion from twice daily NPH by 20 from the previous total daily basal NPH doses. This is particularly important if any episodes of hypoglycemia have been occurring and or there has been a tendency for BGs to be at the lower limit of the patient's target range on the prior intermediate insulin regimen in order to prevent hypoglycemia. If switching from...

Anxiety

A significant literature has addressed the prevalence of anxiety comorbid to DM1. A meta-analysis of 2584 individuals with either DM1 or DM2, found that 14 of the sample showed symptoms of generalized anxiety disorder, and 40 of the sample reported elevated symptoms of anxiety 48 . Although these studies included participants with both types of diabetes, the rates of anxiety were similar for DM1 and DM2. Thirteen percent of young individuals developed an anxiety disorder during the 10 years...

Symptomatic Treatment of Autonomic Neuropathy

As the pathology of DAN can present itself in virtually any organ, the treatment will vary according to the affected organ system and symptoms. While a majority of these symptoms may be addressed with one or more medications, many can be rectified using over-the-counter remedies or lifestyle changes. Gastrointestinal disturbances in T1DM should be approached in a multifaceted approach consisting of glycemic control for prevention or progression of all symptoms, lifestyle changes to minimize...

Insulin Allergy

Allergy to recombinant human rDNA and biosynthetic insulin preparations is a rare complication of insulin therapy. Insulin antibodies of high titers were observed in many patients treated with early insulin preparations containing proinsulin, C-peptide, and other peptide contaminants. Immunoglobulin G-insulin antibodies in very high titers can lead to immune-mediated insulin resistance, which is now extremely rare 91 . Currently, the prevalence of allergic reactions during insulin treatment is...

References

Global prevalence of diabetes Estimates for the year 2000 and predictions for 2030. Diabetes Care 2004 27 1047-1053. 2. National Diabetes Fact Sheet. Center for Disease Control 2005. 3. American Diabetes Association. Standards of medical care in diabetes Position statement . Diabetes Care 2005 28 S4-S36. 4. White P. Pregnancy complicating diabetes. Am J Med 1949 7 609. 5. American Diabetes Association. Gestational diabetes mellitus Position statement ....

Clinical Aspects Of Hypoglycemia

Hypoglycemia constitutes a medical emergency and quick correction is important for survival of the individual. Recovery requires the appropriate glucoregulatory signaling from the brain, an enzmatically and structurally intact liver, and an adequate activation of the ANS and neuroendocrine systems. Normally, this acute physiologic counterregulatory response to hypoglycemia consists of suppression of insulin release and secretion of glucagon, epinephrine, and a host of other glucoregulatory...

Symptomatic Treatment of Peripheral Neuropathy

Pharmacologic Approaches Symptomatic Treatment of Pain Associated with DPN Pain is a common and potentially disabling symptom of DPN. In our practice, we use a stepwise treatment paradigm, titrating a drug to either efficacy within the recommended dose or to the onset of side effects. Table 4 lists the common therapies employed in our clinical practice all have been tested in double-blind placebo-controlled trials reviewed in 1,72,73 . The two therapies in bold are now approved by the Food and...

Hypoglycemia

The normal physiologic response to hypoglycemia includes early suppression of insulin secretion, release of glucagon and catecholamines, and later release of cortisol and growth hormone. It is important to understand that persons with DM1 have alterations in the physiologic suppression of insulin and release of glucagon expected in response to low BG, which impairs ability to return BG levels to normal. These pathophysiologic alterations are present in as few as 5 years after DM1 develops. In...

Pdr

Neovascularization Pdr

NPDR often causes legal blindness with significant residual vision, but PDR can produce rapid, disabling loss of sight. As the retinal environment becomes increasingly hypoxic, the ischemic tissues produce vasoproliferative agents such as vascular endothelial growth factor VEGF in an attempt to attract oxygen-laden blood flow. Lacy, delicate vessels referred to as neovasculariztion begin to proliferate in response Fig. 5 . This often occurs at the optic disc, near ischemic zones of the retina,...

Postprandial Hypoglycemia

Despite careful calculation of carbohydrate intake and insulin doses, continuous glucose sensing reveals that most people with type 1 diabetes experience large glucose fluxes 16 , especially in the postprandial period. Growing evidence suggests that the risk for long-term vascular complications of diabetes may not be entirely explained by average glucose levels, as measured by the A1c 17 . Glycemic exposure, as measured by A1c, age at diagnosis and duration of diabetes explains as little as...

Clinical Presentation And Diagnosis

DPN is a collection of syndromes further categorized as either subclinical class I or clinical class II . Subclinical DPN patients are asymptomatic but have slower NCVs and modest changes on quantitative sensory testing QST . Patients with clinical DPN express symptoms and have abnormalities of either NCV or QST or most frequently both entities. Early diagnosis is imperative as glycemic control is the only proven way to prevent disease progression and the subsequent morbidity of DPN, including...

Info

Phenomenon, Somogyi effect, or incorrect insulin dosing can easily be accomplished by a continuous monitor. In patients who use an insulin pump this is a great way to test and optimize the overnight basal insulin infusion rates. The appropriate use of glucose data, both intermittent and continuous, is essential to the optimal intensive management of diabetes. It has shown the potential to reduce HbAlc, hyperglycemic excursions, and dangerous hypoglycemia. Proper training of the patient in...

Implantable Insulin Infusion Pumps

A surgically implanted programmable pump is available in the European Union EU and is under investigation in the United States. Studies in patients with both DM1 and DM2 have found that this pump system results in glycemic control equivalent to that of MDI injections 105,106 . The implantable pump has the advantage, compared with intensive regimens using injections or external pumps, of a lower incidence of severe hypoglycemia 4 episodes 100 patient-years vs. 33 episodes 100 patient-years with...

Introduction

Diabetic retinopathy DR is the leading cause of blindness in people aged 20 to 74 in industrialized nations 1 . The vast majority of this blindness 95 is preventable with the use of routine screening and the application of evidence-based therapy 2 . Consequently, ophthalmologic screening in diabetics is absolutely critical. DEFINITION, INCIDENCE, PREVALENCE, AND NATURAL HISTORY DR is a progressive retinal microvascular dysfunction and its sequelae are caused by chronic hyperglycemia 2 . Type 1...

Glucose Measurement Accuracy

Blood Glucose Measurement

The performance standards for point-of-care testing of blood glucose have changed over time as the devices improved. Initially, the FDA goal was 15 1986 , but in 1993 the recommendations were updated to 5 6 . The international standard ISO DIS 15197 states 20 , but 20 mg dL for glucose levels less than 100 mg dL 7 . A commonly used analysis is the Clarke error grid 8 . The Clarke error grid assigns a clinical significance to Reference BG Figure 1 Clarke error-grid analysis. Reference BG Figure...

Glucose Monitoring Ac

Intensification of the insulin regimen that may necessitate stepping of goals and further education to enable them to become comfortable with increasing insulin doses. One additional concept that is increasingly recognized as a glycemia-related target is glycemic variability. This measure quantifies variation in BG range over the time period of analysis. The concept of glycemic variability acknowledges the fact that HbAlc is an average of BGs in the 2 to 3 months preceding its measurement and...

Pathogenesis

Hexosamine Ros

Over the past decade, significant progress has been made in uncovering a unifying mechanism underlying the development of both DPN and DAN. Formation of reactive oxygen species ROS as a consequence of continued hyperglycemia is a primary instigator in complication-prone tissue damage 6 . Complication-prone tissues with increased levels of ROS are in a state now commonly referred to as oxidative stress. Hyperglycemic oxidative stress originates in the energy-producing organelles, mitochondria Mt...

Treatment for Comorbid Depression and Diabetes

A few studies have examined the influence of psychopharmacology and psychotherapy on the treatment of depression in this population however data remain scarce. Although the prevalence of major depression and diabetes is well established, there are no large-scale, randomized controlled clinical trials. Both antidepressant medications and cognitive behavioral therapy have demonstrated short-term effectiveness in the treatment of depression among DM individuals. The results seem promising with...

Antecedent Hypoglycemia And Hypoglycemiaassociated Autonomic Failure

Cryer earlier coined the term hypoglycemia-associated autonomic failure HAAF to describe the syndrome of acquired counterregulatory deficits associated with prior hypo-glycemia. This syndrome is experienced by individuals with T1DM and involves blunted neuroendocrine counterregulatory responses to hypoglycemia, lowered glycemic thresholds for activation of counterregulatory defenses, and HU. To test the hypothesis that hypo-glycemia itself causes reduced neuroendocrine and symptomatic responses...

Contributors

Jo Ann Ahern Animas Corporation, West Chester, Pennsylvania, U.S.A. T. S. Bailey Advanced Metabolic Care amp Research, Escondido, California, U.S.A. B. A. Boyer Institute for Graduate Clinical Psychology, Widener University, Chester, Pennsylvania, U.S.A. V. J. Briscoe Vanderbilt School of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University, Nashville, Tennessee, U.S.A. J. M. Cropsey Wills Eye Institute, Philadelphia, Pennsylvania, U.S.A. S. N. Davis Vanderbilt...

Clinical Indications For Betacell Replacement

Given the very limited availability of donated pancreas, which has been estimated to be roughly 4000 to 6000 a year in the United States of America, relatively few patients with diabetes should be considered for beta-cell replacement. There are three general clinical situations that justify this approach. The first is recurrent hypoglycemia with poor symptom recognition despite optimal medical care. This is a complex area to consider. Recurrent hypoglycemia in diabetic patients is a direct...

Classification

Microaneurysm

Early Nonproliferative Diabetic Retinopathy The retina is particularly sensitive to the metabolic changes and ischemia seen in diabetes because it is one of the most metabolically active tissues in the body 8 . Even before clinical or histological evidence of DR begins, retinal pericytes and vascular endothelial cells have already begun to die at an accelerated rate 18 . The first clinically detectable change is microaneurysm formation Fig. 1 . This occurs as capillary walls weaken secondary to...

Insulin Dosing Adjustments And Pattern Management

With experience and close observation of BG results and insulin doses, the health-care provider and the patient can identify patterns that will suggest a need for adjustment in insulin doses to enable attainment of BG targets and A1c goals in the adult DM1 patient who is on an intensive insulin therapy regimen, whether it be with MDI or CSII. Pattern management refers to the practice of reviewing a patient's BG logs, identifying patterns, and or trends where BG is outside or might be expected...

Davison Jm Cheyne Ga. History Of The Measurement Of Glucose In Urine A Cautionary Tale. Med Hist 1974 18 2 194-197.

History of the measurement of glucose in urine A cautionary tale. Med Hist 1974 18 2 194-197. 2. Available at www.mendosa.com history.htm. Accessed on July 30, 2006. 3. The DCCT 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. 4. Heller A. Amperometric biosensors. Curr Opin Biotechnol 1996 7 50-54. 5. Newman JD, Turner APF....

Diet For Ccpd Diabetic Pt

Organ transplantation Kidney transplantation Simultaneous pancreas and kidney transplantation Pancreas after kidney transplantation and tissue matched early so that preemptive transplantation can be done before initiating dialytic treatment. Long-term survival is greatly superior with a kidney transplant than in any dialytic regimen. Although evidence from prospective, controlled, clinical trials is lacking, there is a widespread consensus among nephrologists that diabetic individuals develop...

Physiological Response To Hypoglycemia

The physiologic counterregulatory response to hypoglycemia involves neuroendocrine, ANS, and metabolic processes. This includes the suppression of insulin release as well as secretion of glucagon and pancreatic polypeptide from the pancreas, epinephrine from the adrenal medullae, norepinephrine from sympathetic postganglionic nerve terminals and adrenal medulla, cortisol from the adrenal cortex, and growth hormone from the anterior pituitary gland 11-13 . In humans, inhibition of insulin...

Guidelines For Dosing Correctionsupplemental Insulin

Correction or supplemental doses of insulin CDI are administered to correct hyper-glycemia that results in spite of the patient having taken the usual prescribed basal and prandial insulin doses. CDI is taken in addition to the usual basal and or bolus insulin dose s to be administered at the time when the FS BG is checked and found to be high. The CDI should not be large enough to cause, nor taken so frequently that overlapping peaks insulin stacking will result in hypoglycemia. Typically,...

Traditional Insulin Regimens

The mainstay of management in progestational diabetes in pregnancy has been through the use of regular and NPH insulins. When calculating doses for insulin regimens in type 1 DM, estimate 0.9 U kg day in the first trimester, 1.0 U kg day in the second trimester, and 1.2 U kg day in the third trimester. In insulin regimens for type 2 DM the requirements are increased 0.9 U kg day in the first trimester, 1.2 U kg day in the second trimester, and 1.6 U kg day in the third trimester 35-37 . Insulin...

Adjusting Insulin for Illness or During Periods of Stress Sick Day Rules

Stress and illness clearly impact glycemic control. In the patient with DM1, release of insulin counterregulatory hormones under such circumstances will typically lead to hyperglycemia. Indeed progressive development of hyperglycemia without other aggravating factors may indicate that an illness, e.g., urinary tract infection or viral syndrome is in its prodromal stages. Careful questioning of the patient about symptoms that suggest underlying illness is part of a thorough assessment under...

MDI Insulin Regimen

Long-Acting Basal Insulin Once or Twice Daily with Rapid-Acting Bolus Insulin Before Each Meal This MDI basal-bolus insulin regimen simulates the pattern of insulin production, which occurs physiologically in the person without diabetes. Basal insulin action will most commonly be provided by insulin glargine or detemir. Insulin glargine will generally be given once daily for control of fasting and premeal glucose levels. This dose is given at the same time daily and may be delivered either at...

Practical Guidelines for Calculation of Insulin Doses for the MDI Regimen

When undertaking calculation of insulin doses for initiation of therapy for any insulin regimen, one must be cognizant of the variability in total daily insulin requirements among individuals and within a given individual, and of the variation in a given insulin's lag time to onset of action, time to peak, and duration of action. It is also necessary to be aware in the event of making a switch from one type of regimen to another of the level of BG control prior to the time of change. In all of...

Specific Practical Guidelines For Pattern Management Core Insulin Adjustment Guidelines

Core insulin adjustment guidelines will address basic recommendations for correction of hypoglycemia, hyperglycemia, variations in food intake or level of physical activity, and days when the patient is sick or stressed. When glycemic control is suboptimal and both hyperglycemia and hypoglycemia are present, one should first address hypoglycemia and correct it. This approach is recommended for several reasons. First and foremost, the short-term hypoglycemia is a safety issue. In addition, if...

Insulin Adjustment Guidelines

Insulin adjustment is an art that should be guided by the science of what is known about how each component insulin of the total daily insulin requirement acts and how lifestyle and other variables impact BG levels. Insulin adjustment guidelines are grounded in a sound knowledge of the pharmacokinetics of insulin, as discussed earlier in this chapter. When BG levels are outside target ranges and it is determined that an adjustment in insulin dosing is necessary, knowledge of the action curves...