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 FirstLine 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...
Potassium Bicarbonate and Phosphate
Even though the body is potassium depleted, with a typical deficit of around 5 mmol kg, initial potassium values are usually normal or elevated. Insulin therapy, rehydration and correction of acidosis all cause a decrease in serum potassium and 20-30 mmol potassium h may be administered once potassium levels are below 5.0 mmol L, provided renal function is intact. Subsequent potassium administration is guided by frequent concentration measurements adjuvant oral administration may be used in...
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...
References 1
1. The IDF E-atlas. Issued at www.eatlas.idf.org by International Diabetes Federation IDF , Avenue Emile De Mot 19, B-1000 Brussels, Belgium. 2. Beran D, Yudkin JS. Diabetes care in sub-Saharan Africa. Lancet 2006 368 1689-1695. 3. Gale EA. Dying of diabetes. Lancet 2006 368 1626-1628. 4. Rungby J, Brock B, Schmitz O. New strategies in insulin treatment analogues and noninvasive routes of administration. Fundam. Clin. Pharmacol. 2005 19 2 127-132. 5. Riley S. The Diabetes Market Outlook to...
The Global 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...
Comparison of Biphasic Premix Insulin Analogues with Biphasic Premix Human
Several new biphasic premix insulin analogues have been introduced during the last years. Novomix 30, contains 30 rapid-acting aspart and 70 protamin - crystallised aspart. HumaLog Mix 25 , contains 25 rapid-acting lipro and 75 protamine-crystallised lispro. Biphasic premix analogues are available in other differently proportioned premix preparations, but these are used less frequently. The new premix insulin analogues can be injected immediately before a meal and the peak insulin concentration...
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,...
Edwin Gale Bristol UK
Why should anyone bother to put a textbook together I have often wondered about this, even while doing the job myself. All those who have engaged in this activity will tell you that the work will be harder than you can imagine, that chasing reluctant authors is a depressing business, and that there are easier ways of making money. Worse still, the book you produce will typically have many competitors, and is destined to suffer from built-in obsolescence. All these are questions for those who...
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 BorchJohnsen
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,...
Comparison of Premix Insulin Analogues with LongActing Insulin Analogues
In a 28-week study 209 subjects treated with OADs except secretagogues were randomised to BIasp 30 70 twice-daily or insulin glargine at bedtime and titrated to target blood glucose 4.0-5.5 mmol L before breakfast and dinner for biphasic premix aspart Blasp and before breakfast for insulin glargine by algorithm-directed titration 23 . At the end of the study HbAlc was lower in Blasp 30 70 than in the glargine group 6.9 1.2 vs. 7.4 -1.2 , especially for subjects with baseline HbAlc gt 8.5 . More...
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
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
1. Reaven GM. Banting lecture 1988. 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...
SelfMonitoring 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
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...