Lowering the Threshold for IFG What are the Consequences

The most recent revision of the diagnostic criteria for IFG by ADA 6 lowered the diagnostic threshold for IFG 6.1-5.6, so now the diagnostic interval for IFG according to ADA is 5.6-6.9. The major reason for redefining IFG was an attempt to improve the alignment of IFG and the corresponding intermediate category based on the oral glucose tolerance test impaired glucose tolerance (IGT) in predicting the future development of type 2 diabetes. The proposed new diagnostic threshold is derived from...

Type Diabetes

In the majority of subjects type 2 diabetes is usually not well controlled by lifestyle modifications and so presents major challenges to pharmacother-apy. The increasing number of ways to attack the cardinal metabolic defects of type 2 diabetes -insulin resistance and beta-cell failure - leaves patients and doctors with numerous possibilities for pharmacological interventions. The forecast of increased prevalence of diabetes in the coming years raises enormous ethical and practical questions,...

Improvement of Cardiovascular Risk Profile by Metformin

During the last two decades a number of studies showed beneficial effects of metformin on traditional and non-traditional cardiovascular risk factors 11,47-58 . Metformin reduces fasting and postprandial insulin levels 3 , insulin resistance 4-6 and has beneficial effects on lipids, thrombosis and blood flow. Metformin has a weight-lowering effect 11,13,15 and reduces hypertriglyceridaemia 11 , elevated levels of PAI-1 47 , factor VII 49 , C-reactive protein 51,52,54 and intact proinsulin and...

Side Effects Contraindications and Safety of Metformin

Gastrointestinal side effects, including abdominal discomfort and diarrhoea, are the most common adverse events, occurring 10-15 of patients, depending on the dose 1,8,11 . These side effects usually improve with continued use and are minimal if started at a low dose (e.g. 250-500 mg d) and slowly titrated upward. Discontinuation of therapy because of side effects occurs in less than 4 of patients. Because metformin does not increase insulin secretion 3 , biochemically documented hypogly-caemia...

Insulin Pump Treatment or Continuous Subcutaneous Insulin Infusion

Insulin pump therapy started in UK in 1976. Insulin pumps deliver a continuous basal insulin infusion (CSII) and patient-activated bolus doses at meal times. The pump is attached to the patients by an infusion set consisting of long flexible tubing with a needle or catheter on the end and is inserted subcuta-neously in the patient. In two meta-analysis CSII was compared with conventional insulin treatment 29,30 , which is not the actually used MDI. CSII caused a significant reduction in HbA1C...

References

Stovring H, Andersen M, Beck-Nielsen H, et al. Rising prevalence of diabetes evidence from a Danish pharmaco-epidemiological database. Lancet 2003 362(9383) 537-538. 2. Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35) prospective observational study. BMJ 2000 321(7258) 405-412. 3. Liebl A, Mata M, Eschwege E. Evaluation of risk factors for development of complications in Type II diabetes in Europe....

Renal Effects

PPARy is expressed in the rat kidney, primarily in the collecting ducts 43 . Its presence in this location suggests that it may be involved in water and sodium retention 44 . It has also been detected in the mesangial cells of rats 45,46 . All of the thiazolidinediones used clinically have been shown to delay the onset of proteinuria or reduce established proteinuria 16,45-47 . In a small randomized study, pioglitazone significantly reduced urinary albumin excretion from 142.8 to 48.4 mcg...

Changes in Body Weight

SU treatment is usually associated with weight gain, usually from 2 to 5 kg, which is problematic in a group of patients already overweight 10,11,46 . However, this effect is also commonly seen during treatment with insulin and thiazolidinediones. Compared with the latter, the increase in body weight observed at SU treatment seems to be less 9,42 . In the UKPDS, mean body weight changes ranged from 1.7 kg (glibenclamide) to 2.6 kg (chlorpropamide). Nevertheless, this undesirable effect was...

Precipitating Factors

Unless related to omission of insulin therapy, DKA is usually precipitated by coexisting illness. The most common factor is infection ranging from trivial viral infections to full-blown septicaemia. Other precipitating factors are cardiovascular events (myocardial infarction, stroke), gastrointestinal disease, inflammatory diseases, pancreatitis, trauma and major surgery, alcohol abuse and drugs (e.g. glucocorticoids). All of these factors induce insulin resistance due to stress hormone...

Clinical Efficacy of Metformin HbAlc Lowering But No Weight Gain

In placebo-controlled trials, metformin lowered HbAlc concentrations by about 1.0-2.0 8,9 . The efficacy of metformin monotherapy was equivalent to the monotherapy of sulfonylurea or thiazoliden-diones 10,11 . The greatest advantage of metformin compared with other anti-diabetic agents (insulin, sulfonylureas or thiazolidendiones) has been the fact that it is associated with weight loss but not with weight gain 1,9-14 . This has been shown for drug-nai've patients as well as for patients...

Summary

GLP-1 is an intestinal incretin hormone that stimulates insulin (incretin) and suppresses glucagon secretion, inhibits gastric emptying, and reduces appetite and food intake. In contrast to the other incretin hormone, GIP, GLP-1 remains active in patients with type 2 diabetes. GLP-1 itself, however, cannot be used for therapeutic purposes because of its rapid proteolytic degradation and inactivation (DPP-4) and renal elimination, leading to a t1 2 of 1-2 min. Therapeutic use of the antidiabetic...

Introduction

Approximately 70 years ago Himsworth and colleagues completed a series of elegant experiments demonstrating for the first time the importance of insulin resistance in human disease 1-5 . The results of their experiments challenged the prevailing dogma that all cases of human diabetes could be explained by a deficiency of insulin, and suggested, a state of diabetes might result from inefficient action of insulin as well as from a lack of insulin. Furthermore, they proposed that diabetes could be...

Sulfonylurea

In 1942, the first sulfonylurea (SU) VK 57 was investigated in the Section of Infectious Diseases, Montpellier Hospital, France 9 . A few years later, that compound was shown to induce neoformation of insulin granules in rat beta cells. Since 1954 SUs (Fig. 1) have been available in the USA 10 and for many years they have been remained the most popular pharmacological drug in the treatment of diabetes mellitus. First-generation SUs include chlorpropamide, tolbutamide, tolazamide and...

How Does Triple Therapy Improve Glucose Metabolism

First of all, insulin aspart given at the initiation of the meal was in fact able to reconstruct the necessary fast and high insulin peaks compared with non-diabetic subjects (Fig. 3). This seems to be important since the insulin concentration obtained (24-h area under the curve) is much lower in triple therapy despite much lower blood glucose values. This indicates that the insulin profile is more important than the absolute amount of insulin given. We were able to measure insulin aspart with...

The Role of the Liver in Fasting and Postprandial Glycaemia

Blood glucose is determined by the rate of glucose appearance (Ra) and the rate of glucose disappearance (Rd). An increase in Ra or a decrease in Rd (or both) may result in hyperglycaemia. Glucose appearing in blood can derive from both ingested carbohydrates and the endogenously produced glucose from liver and kidneys. Most focus has been on the basal hepatic glucose production (HGP), as for several years HGP, alone, was claimed to determine fasting blood glucose values in the morning. This...

Management

Management and treatment of DKA rests on four pillars 1. Fluid and electrolyte therapy. 2. Intravenous insulin therapy. 3. Treatment of co-morbidities. 4. Careful monitoring of the clinical course. It is particularly important that treatment is initiated without delay and that the patient is monitored frequently and carefully, preferably in a highly specialised unit. Severe cases should be treated and monitored in intensive care unit, where possible. Useful algorithms for treatment are...

Contents

Section Dedication and Introduction by Carl Erik Mogensen v xiii 2. New Definitions of Diabetes 9 Section Pharmacotherapy of Diabetes 3. The Insulin Resistance Syndrome Concept and Therapeutic Approaches 19 4. Medical Emergencies - Diabetic Ketoacidosis and Hyperosmolar Hyperglycaemia 31 Niels M0ller and K. George M.M. Alberti 5. Notes on the Use of Glucagon in Type 1 39 6. Insulin and New Insulin Analogues, Insulin Pumps and Inhaled Insulin 7. Insulin and New Insulin Analogues with Focus on...

Treatment with NPH Insulin and the Long Acting Insulin Analogues

One treatment concept has gained popularity in recent years following its success in clinical trials the addition of a long-acting basal insulin formulation to an existing oral antidiabetic drug (OAD) treatment, followed by aggressive titration of the insulin dose to achieve target levels of glycemia. Adding basal insulin has been shown to lower the entire 24-h blood glucose profile, and in combination with metformin the increase in weight after initiation of insulin treatment has been...

Thiazolidinediones in Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is characterized by menstrual irregularities, infertility, hyperandro-genism, obesity, and insulin resistance. In a study of rosiglitazone (4 mg twice daily for 2 months) with or without clomiphene in 25 women with PCOS who had not responded to clomiphene alone, ovulatory rates were higher in the combined versus monotherapy groups (77 and 33 , respectively) 53 . Pioglitazone has also been shown to improve ovulation rates and hyperadrogenism associated with PCOS....

Conclusion

Insulin-mediated glucose disposal varies widely in the population at large, with approximately 50 of the variability in insulin action resulting from differences in lifestyle variables with degree of adiposity and physical fitness each accounting for approximately (25 ). The remaining 50 is familial, likely to be of genetic origin, with powerful ethnic differences. Type 2 diabetes develops when insulin-resistant individuals cannot secrete the increased amounts of insulin needed to overcome the...

Open Questions by

With the recent publication from WHO and IDF on definition and diagnosis of diabetes mellitus and intermediate hyperglycaemia 4 , a natural question could be - have we now reached the end of the road Unfortunately, the only possible answer is a no. Science is progressing, and as part of this, our understanding of the underlying aetiology and pathogenic mechanisms behind abnormalities in glucose metabolism will improve. Definition and classification of diseases must (or at least should) always...

Cardiac Effects of GLP Consequences of the Treatment with Incretin Mimetics and DPP Inhibitors

The GLP-1 receptor is expressed in the heart 56 . In GLP-1 receptor knock-out mice structural and functional cardiac abnormalities are typical 217 . In animals, exposure to GLP-1 reduces the size of myocardial necroses in the case of induced infarction 218 . In a pilot study with patients treated for acute myocardial infarction, a 48-h infusion of GLP-1 improved left-ventricular function and a wall-motility index 219 . In a dog model of dilated cardiomyopathy, GLP-1 increased glucose uptake and...

Hypoglycemia

Since the thiazolidinediones work independently of the pancreas, and typically reduce insulin levels in patients with type 2 diabetes, there is very little, if any, clinical risk of hypoglycemia with these agents. However, when circulating insulin levels are increased, such as in patients taking a sulfonylurea or insulin, the addition or pioglitazone or rosiglitazone may result in hypo-glycemia. This is usually apparent after four or more weeks of therapy, since it takes few months for the full...

Availability

Varying with socioeconomics and health policies, the availability of oral or injectable antidiabetic agents varies. However, basic drugs for beta-cell stimulation, the sulphonylureas, and for treating insulin resistance and increased hepatic glucose output (the biguanides) remain cheap, effective and widely accessible. Alpha-glucose inhibitors and, in particular, thiazolidinediones, retarding the rates of intestinal glucose absorption and tissue insulin resistance, respectively, are...

Discontinuation of Treatment

With randomized clinical trials concerning incretin mimetics and DPP-4 inhibitors lasting up to 1 year 125,155 , and open-label follow-up reported up to 2 years 183 , it is obvious that these studies cannot provide an estimate of how long treatment with incretin mimetics and DPP-4 inhibitors can meaningfully control glycemia. It is, however, obvious that not all patients treated with such agents achieve their glycemic target, even within the time frame of the studies that have been reported....

Pharmacological Interventions

There are three pharmacological agents often referred to as insulin sensitizers two thiazoli-denedione (TZD) compounds (rosiglitazone and pioglitazone) and metformin. Despite the frequency with which this term is applied to metformin, in the absence of weight loss, insulin-stimulated glucose disposal does not increase in metformin-treated individuals 59-61 . It is outside the province of this chapter to discuss the mechanism of action of met-formin, nor its use as an effective treatment of type...

Weight Loss

It has been clear for more than 30 years that overweight obese individuals are more likely to be insulin-resistant hyperinsulinemic, and that weight loss in these individuals will improve insulin sensitivity, associated with lower plasma insulin concentrations and an improved lipoprotein phenotype 39 . It is now well-recognized that a variety of metabolic abnormalities improve when overweight obese individuals lose weight, and that this intervention can lead to substantial clinical benefit. For...

Insulin Resistance Hyperinsulinemia and the IRS

Insulin resistance is not a disease, but a physiological abnormality that increases the likelihood that one or more of the abnormalities listed in Table 2 will be present. Furthermore, because the abnormalities seen in Table 2 occur more commonly in insulin-resistant individuals, they are at increased risk to develop one or more of the clinical syndromes listed in Table 3. However, the relationship between insulin resistance and the changes seen in Tables 2 and 3 is complicated, and the...

Pioglitazone and Macrovascular Disease

A recent study 31 investigated the effects of intensive glycemic control on macrovascular disease. It was a prospective, randomized controlled trial involving over 5,000 type 2 diabetics with preexisting macrovascular complications. They were randomized to receive either 45-mg pioglitazone or placebo for approximately 2.5 years. Pioglitazone was shown to reduce the risk of all cause mortality, non-fatal myocardial infarction (excluding silent myocardial infarction), and stroke by approximately...

Measures to Assure Metabolic Control Self BloodGlucose Monitoring

Although exenatide was approved by the FDA and introduced for use in the USA in 2005 (and other countries since) and sitagliptin has been approved in the USA and elsewhere in late 2006, no recommendations regarding metabolic control have been issued. The following suggestions, therefore, are based on the known properties of incretin mimetics and DPP-4 inhibitors. Since incretin mimetics will be used at fairly standardized doses (vide supra), and not based on individual titration (like in the...

Insulin Detemir Levemir

In insulin detemir (B29lys(epsilon-tetradconoyl), des B30 human insulin) a 14-C fatty chain has been attached to position B29 and the amino residue at position B30 has been omitted 11,27 . When injected subcutaneous it dissociates exposing the fatty free acid chain, which subsequently binds to the free fatty acid binding sites on the albumin molecule 11,27 . Insulin detemir is 98-99 albumin bound in human plasma 11,27 . It is only the free fraction of detemir that is biologically active. The...

Trends in the Use of Antidiabetic Drugs

A recent survey 11 of antihyperglycaemic drugs in ten European countries showed that their use increased in all countries but with very different treatment patterns. The use of insulin doubled from 1994 to 2003 in some countries (England and Germany) but remained stable in others (Belgium, Portugal, Italy). The use of biguanides increased substantially, whereas the use of sulphonylureas increased more moderately in most countries. Insulin accounted for more than 50 of the daily antidiabetic...

The Market for Antidiabetic Agents for Type Diabetes

Including insulin, half of the global diabetes market is accounted for by the USA. Other major markets are Germany (7 ), the UK (4 ) and France (3 ). Highly populated countries with substantial numbers of people with diabetes such as Russia and Brazil each account for approximately 1 of the market. The market is dominated by (54 ) original branded drugs however, generics account for some of the market and unknown numbers of patients are treated with generics in countries such as China and India...

Mechanism of Action

Thiazolidinediones bind and activate the nuclear receptor peroxisome proliferator-activated receptor-Y (PPARy). This receptor is expressed predominantly in adipocytes, where it regulates adipocyte differentiation and the expression of adipocyte-specific genes 1 . It is expressed in lower levels in muscle and liver tissue 2 and has also been identified in several other tissues (discussed below). Based on affinity for PPARY, rosiglitazone is a more potent PPARY ligand than pioglitazone. The...

Possible Effects of Incretin Mimetics and DPP Inhibitors on pCell Mass

Both type 1 and type 2 diabetes are caused by a significant deficit in P-cell mass, caused by increased P-cell apoptosis 193-195 . Strategies to inhibit P-cell apoptosis and or increase the rate of P-cell replication may therefore allow for the prevention or even reversal of diabetes 196 . A number of studies have suggested that GLP-1 might exhibit such properties. Thus, in P-cell lines (INS-1 cells), GLP-1 increased the rate of proliferation through induction of phosphatidylinositol 3-kinase,...

Diagnosis and Clinical Presentation

DKA usually develops over a short period of time, generally in less than 24 h. There may have been some antecedent days with general malaise and poor metabolic control. Depending on the degree of hyperglycaemia, the history will include symptoms of polydipsia and polyuria. Specific symptoms depend on precipitating factors and co-morbidity. Physical examination may reveal poor skin turgor, hyperventilation (Kussmaul), hypotension, tachycardia and impairment of mental status. Many patients have...

GLP Receptor Agonists

Exenatide Liraglutide Sitagliptin

Exenatide synthetic exendin-4 was isolated from the salivary gland of the gila monster, a lizard found in the deserts of Arizona 117 . Due to an 50 amino acid homology with native human GLP-1 Figs. 1 and 4 , this peptide acts as a potent agonist at the mammalian GLP-1 receptor, but is not substrate to proteolytic cleavage by DPP-4 117 . This leads to a circulating plasma half-life of 2-4 h, with exenatide levels being raised for 6 h after a single subcutaneous injection 118 . The clinical...

Lipid Metabolism

Contrary to popular belief deranged lipid - not carbohydrate - metabolism is the main cause of DKA. In essence DKA is caused by uncontrolled lipolysis in adipose tissue and uncontrolled ketogenesis in liver. Adipose tissue is present in regional depots such as subcutaneous upper and lower body and visceral fat 11 . Apart from these classic depots fat is present in most other tissues, for example, connective tissue, bone marrow, liver and muscle. The picture is further complicated by the fact...

Kjeld Hermansen

Keywords Insulin, insulin analogues, basal bolus insulin treatment, continuous subcutaneous insulin infusion, insulin pump, inhaled insulin, type 1 diabetes mellitus. The microvascular complications of type 1 diabetes mellitus T1DM were rarely noted before the discovery of insulin. The introduction of insulin therapy allowed patients to live long enough to develop diabetic retinopathy and diabetic nephropathy 1 . It was discussed extensively whether these complications were caused by...

Choice of Patients

Since incretin mimetics are injectable antidiabetic drugs, their use will most likely be considered, when oral antidiabetic agents in combinations do no longer assure glycemic control of the required quality. This is the moment, when - according to current guidelines - the start of insulin treatment would be considered according to most recommendations 166,167 . However, such guidelines have, until now, not considered the availability of incretin mimetics or DPP-4 inhibitors. An attempt has...

Pathogenesis and Pathophysiology

In DKA the major culprit is insulin deficiency. Insulin deficiency may be relative, for example, in the setting of severe infection, where normal amounts of insulin are insufficient or absolute when insulin therapy is neglected. At some stage insulin deficiency becomes coupled with an excess of counter-regulatory hormones and cytokines 9,10 . The traditional catabolic stress hormones include glucagon, epinephrine, Table 1. Classification of clinical pictures and diagnostic criteria adapted from...

Metformin in Combination Therapy

Many studies have shown that metformin can be used in combination with all available anti-diabetic drugs including sulfonylureas, glinides, a-glucosidase-inhibitors, thiazolidendiones, DPP-4 inhibitors as well as with injection of insulins and GLP-1 agonists 9,13,24-29 . The combination of metformin and sulfonylureas is the most common oral combination therapy and is used by about 50 of all type 2 diabetic patients. During the last years many other oral combination therapies were studied and...

Metformin as First Line Pharmacotherapy of Type Diabetes

A recently published consensus statement from the American Diabetes Association ADA and the European Association for the Study of Diabetes EASD suggested using metformin as first-line pharmacotherapy not taking into account clinical characteristics such as obesity or body weight 22 . The authors recognized that for most individuals with type 2 diabetes, lifestyle interventions failed to achieve or maintain metabolic goals, either because of failure to lose weight, weight regain, progressive...

Carl Erik Mogensen

Hypoglycaemia may be an important complication in the treatment of type 1 diabetes. When intravenous glucose is available, glucagon has no place in the treatment and certainly also many patients may be treated with glucose or sweet foods given orally. However, if the patients are not conscious or acting negatively, glucagon used intramuscularly or subcu-taneously is important in a dose of 1-2 mg 1-3 . Glucagon acts by activating the enzymes in hepatic cells that increase glycogenolysis and...

The Global Insulin Market

Insulin Market

Sales of rapid-acting analogues of insulin now exceed those for human sequence insulin. Humalog and Novolog Novorapid had combined sales totalling US 1555.2 million in 2005 compared with US 870.2 million for all other rapid-acting insulins, Humalog being the market leader. The intermediate-acting insulins, Humulin and Novolin Insulatard being the dominant examples, sold US 1050.8 million in 2005, which was a small decrease compared with 2004. The market US 1576.8 million in 2005 for...

DPP Inhibitors

The therapeutic use of GLP-1 is primarily limited by its rapid in vivo degradation by the enzyme DPP-4 37,38,138 . DPP-4 is a ubiquitous membrane-spanning cell-surface amino-peptidase widely expressed in many tissues including liver, lung, kidney, intestinal brush-border membranes, lymphocytes, and endothe-lial cells, which can also be found circulating in plasma 39,139,140 . DPP-4 nonspecifically cleaves peptides displaying a proline or alanine residue in the second amino-terminal position,...

Therapeutic Potential of Incretin Hormones

Owing to their pivotal role in the postprandial regulation of insulin secretion, both GIP and GLP-1 have been suggested as potential antidiabetic drug candidates 4,98 . However, no significant reduction in glycemia could be achieved in studies with intravenous infusions of the GIP in hyperglycemic patients with type 2 diabetes 99 . Indeed, while GIP exhibits potent insulinotropic properties in healthy subjects and probably mediates the major proportion of the incretin effect under physiological...

Knut Borch Johnsen

Keywords Diagnosis, IFG, IGT, classification, definitions. In 1980, the World Health Organisation WHO ended a long phase of confusion by providing international standards for diagnosis and classification of diabetes 1 . Before this, confusion existed with respect to the glucose threshold for diagnosis of diabetes and other categories of glucose intolerance as well as the glucose load used for the oral glucose tolerance test. As always, however, new scientific data and insight combined with...

Inhaled Insulin

Subcutaneous injection has been the only route of insulin administration for daily use by patients with T1DM for the past 80 years. A barrier to insulin therapy relates among other things to patient fears and anxiety about insulin injections. Although needles have become smaller and sharper, thereby causing less painful injections some people consider needles and injections a perceived stigma for diabetic subjects. It is only recently that alternative routes of insulin administration are...

Contributors

Department of Endocrinology, Odense University Hospital, Kloevervaenget 6, 4, 5000 Odense C, Denmark, Department of Ophthalmology, rhus University Hospital, DK-8000 rhus C, Denmark, toke.bek mail.tele.dk Department of Medicine, University College London Medical School, 5 University Street, WC1 6JJ London, UK, rmhajbe ucl.ac.uk Universities of Manchester, UK, Miami, FL, USA Consultant Physician, Manchester Royal Infirmary, Manchester, UK, ABoulton med.miami.edu Director Steno Diabetes Center,...

Pharmacoepidemiology of Diabetes Safety Considerations

While phase 1 and 2 trials are necessary for the demonstration of early safety in humans, phase 3 trials randomized controlled trials are unsurpassed in design for the demonstration of the effects of a drug on the disease course efficacy . Post-marketing phase 4 trials vary in design however, they are often not suited to evaluate therapeutic effects effectiveness in the population as a whole and long-term safety in non-selected groups of patients. Pharmacoepidemiology offers methods,...

Secretion and Action of Incretin Hormones in Physiology

Glp Receptor Physiology

Physiological Roles of Gastrointestinal Peptide Hormones The ingestion of nutrients elicits the secretion of gastrointestinal hormones intimately involved in the regulation of gut and gallbladder motility, digestive juice secretion, and postprandial carbohydrate metabolism. In particular, incretin hormones stimulate insulin secretion from the endocrine pancreas. Through the action of incretin hormones, enteral nutrition provides a more potent insulinotropic stimulus relative to an isoglycemic...

Diabetes.1995 44 11 1249-1258

Role of insulin resistance in human disease. Diabetes 1988 37 12 1595-1607. 2. Polonsky KS. Lilly lecture 1994. The beta-cell in diabetes from molecular genetics to clinical research. Diabetes 1995 44 6 705-717. 3. Weyer C, Tataranni PA, Bogardus C, Pratley RE. Insulin resistance and insulin secretory dysfunction are independent predictors of worsening of glucose tolerance during each stage of type 2 diabetes development. Diabetes Care 2001 24 1 89-94. 4....

Reclassifying Diabetes How to Differentiate Between Type and Type Diabetes

So far the focus on the 1997 ADA and 1999 WHO revision of the diagnostic criteria has been on the impact of the revised diagnostic thresholds. Another often neglected but equally or even more important revision relates to the classification of patients. In 1985, patients were classified as having insulin-dependent IDDM and non-insulin-dependent NIDDM diabetes based on the underlying disease, that is, whether beta-cell dysfunction was reduced to a level where insulin was needed to survive...

Hyperosmolar Hyperglycaemia

Hyperosmolar hyperglycaemia HH is generally the fulminant result of poorly treated type 2 diabetes or delayed diagnosis of previously unknown type 2 diabetes. HH is less frequent than DKA, but mortality is higher and remains close to 15 in many centres 1,20 . As implied hyperosmolality is the primary clinical problem and there will be hyperglycaemia of gt 35-40 mmol L and an effective serum osmolality of gt 320 mOsm kg Table 1 . HH most often occurs in frail patients in combination with other...

Self Monitoring of Plasma Glucose HBGM

Self-monitoring of plasma glucose HBGM is fundamental to diabetes care 27,28 . Frequent monitoring facilitates improved glycaemic control, avoidance of hypoglycaemia and lifestyle flexibility when results are used to assist the individual in their dietary choices, physical activity and insulin doses. HBGM should be carried out three or more times daily in T1DM on MDI and at least four times daily on insulin pump treatment. To achieve postprandial glucose targets, postprandial HBGM may be...

Conventional Intensified Insulin Therapy or Multiple Daily Insulin Injections MDI

Nph Insulin Half Life

In conventional intensified insulin therapy MDI using the basal-bolus approach with MDI, continuous basal insulin supply is obtained by once- or twice-daily subcutaneous injections of longer-acting preparations, supplemented by mealtime injections of more rapid-acting formulations. These include structurally unchanged regular insulin preparations and short-acting insulin analogues SIAs , which dissociate more rapidly than regular insulins and are absorbed faster. The glucose-lowering effect of...

Cardiovascular Implications

SUs bind to a subunit of the KATP channel complex inducing closure of the channel. In the past years, different cross-reactivity with cardiovascular KATP channels have been investigated 50 . Particular attention has been set on the phenomenon of ischemic preconditioning, which self protects the myocardial cells from ischemia and reduces infarct size 51 . As preconditioning is a result of opening the KATP channels, it could be opposed by closing these channels, a fact that raised concerns about...