ReviewType 2 diabetes mellitus: epidemiology, pathophysiology, unmet needs and therapeutical perspectivesDiabète de type 2 : épidémiologie, physiopathologie, problèmes non résolus et perspectives thérapeutiques
Section snippets
Epidemiology of type 2 diabetes in France
In 2007, type 2 diabetes represents a major public health issue all over the world, becoming a “diabetes epidemic” as stated by Zimmet [1]. A few years ago, the concern of the “diabetes epidemic” was restricted to the US while the other parts of the world were not considered as threatened. Unfortunately, the picture has moved and nowadays no country escapes the diabetes invasion. In the world, diabetes prevalence in adults aged 20 and over was 4.0% in 1995 and it is expected to increase to 5.4%
Abnormalities in insulin secretion
According to WHO, type 2 diabetes is defined as resulting from a defect in both insulin secretion and in insulin sensitivity. β-cell dysfunction includes abnormalities in pulsatility and in kinetics of insulin secretion, quantitative and qualitative abnormalities of insulin, β-cell loss and its progression.
Therapeutic overview: present and perspectives
Appropriate diet, weight reduction and physical activity are the cornerstones of the treatment of type 2 diabetes, but the achievement of optimal glycaemic control, which is essential for the prevention of diabetes related complications, generally requires the use of antidiabetic drugs. None of these are able to correct all the anomalies involved in the pathogenesis of type 2 diabetes. So, they generally fail after a few years of evolution of the disease [56]. Combination therapies and even
DPP-IV inhibitors
These inhibitors of dipeptidyl peptidase-IV (DPP-IV) have been recently launched in the US and will be soon on the European market after many large preclinical and clinical studies (mainly three pharmaceutical companies and drugs: sitagliptin vildagliptin and saxagliptin). DPP-IV inhibitors stabilize endogenous GLP-1 at physiological concentrations, and induce insulin secretion in a glucose-dependent manner; therefore, they do not demonstrate any hypoglycaemic effects since their effects, on
Long-acting GLP-1 analogues, and GLP-1-receptor agonists
Long-acting glucagon-like peptide 1 analogue (liraglutide), and GLP-1-receptor agonists (exenatide) are more powerful on glycaemic control compared to DPP-IV inhibitors. Effect of GLP-1 analogues starts later, after a few weeks, and produces a more marked benefit on weight. However, DPP-IV inhibitors compared with GLP-1 analogues are orally administered and cause little effects on gastric emptying, and subsequently few or no gastrointestinal side effects.
Conclusion
If one considers the international guidelines and the clinical results obtained with DPP-IV inhibitors, it is possible to suggest their integration in the following way. Admittedly, whether in the future, one can imagine DPP-IV inhibitors as an alternative first line of treatment for type 2 diabetes, metformin will probably remain, for years, the most evidence-based, recommended, less expensive and most used first line OAD. Long-term studies considering safety, durability on glycaemic effects
References (125)
The burden of type 2 diabetes: are we doing enough?
Diabetes Metab
(2003)- et al.
The prevalence and cost of diabetes in metropolitan France: what trends between 1998 and 2000?
Diabetes Metab.
(2003) - et al.
Insulin deficiency in non-insulin-dependent diabetics
Lancet
(1989) - et al.
β-cell dysfunction, rather than insulin-insensitivy, is the primary defect in familial type 2 diabetes
Lancet
(1986) - et al.
Etiology of insulin resistance
Am. J. Med.
(2006) - et al.
Glucose transporters and diabetes
Semin. Cell Dev. Biol.
(1996) Meglitinide analogues: a review of clinical data focused on recent trials
Diabetes Metab.
(2006)- et al.
Repaglinide versus glyburide: a one-year comparison trial
Diab. Res. Clin. Pract.
(1999) - et al.
A comparison of glycemic effects of glimepiride, repaglinide, and insulin glargine in type 2 diabetes mellitus during Ramadan fasting
Diab. Res. Clin. Pract.
(2007) - et al.
Thiazolidinediones for the treatment of type 2 diabetes
Eur. J. Intern. Med.
(2007)
Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomized controlled trial
Lancet
Global prevalence of diabetes: estimates for the year 2000 and projections for 2030
Diabetes Care
Treated diabetes in France: what trends between 2000 and 2005?
Diabetes Metab.
Assessment of diabetes screening by general practitioners in France: the EPIDIA Study
Diabet. Med.
Effects of traditional and western environments on prevalence of type 2 diabetes in Pima Indians in Mexico and the US
Diabetes Care
Prévalence de l’obésité de l’adulte en France. La situation en 2000 à partir des résultats des études OBEPI
Ann. Endocrinol. (Paris)
Épidémiologie des complications liées au diabète
Rev. Prat. (Paris)
Abnormal patterns of insulin secretion in non-insulin-dependent diabetes mellitus
N. Engl. J. Med.
Impaired pulsatile secretion of insulin in relatives of patients with non-insulin-dependent diabetes
N. Engl. J. Med.
The plasma insulin response to glucose infusion in healthy subjects and in diabetes mellitus
Acta. Endocrinol. (Kbh)
Confirmation of impaired early insulin response to glycemic stimulus in non-obese mild diabetes
Diabetes
Effect of loss of first-phase insulin secretion on hepatic glucose production and tissue glucose disposal in humans
Am. J. Physiol.
Causal linkage between insulin suppression of lipolysis and suppression of liver glucose output in dogs
J. Clin. Invest.
Biphasic insulin secretion during intravenous glucose tolerance test promotes optimal interstitial insulin profile
Diabetes
Quantitative and qualitative changes in the early insulin response to glucose in subjects with impaired carbohydrate tolerance
Diabetes Care
Early metabolic defects in persons at increased risk for non-insulin-dependent diabetes mellitus
N. Engl. J. Med.
Radioimmunoassay may overestimate insulin in non-insulin-dependent diabetics
Clin. Endocrinol. (Oxf.)
UK Prospective Diabetes Study 16. Overview of 6 years therapy of type II diabetes: a progressive disease
Diabetes
Onset of NIDDM occurs at least 4–7 years before clinical diagnosis
Diabetes Care
Glucose toxicity
Diabetes Care
Lipotoxicity in the pathogenesis of obesity-dependent NIDDM: genetic and clinical implications
Diabetes
Glycation-dependent, reactive oxygen-species-mediated suppression of the insulin gene promoter activity in HIT cells
J. Clin. Invest.
Islet amyloid and type 2 diabetes mellitus
N. Engl. J. Med.
Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islets of Japanese type II diabetic patients
Diabetologia
β-cell deficit and increased β-cell apoptosis in human with type 2 diabetes
Diabetes
β-cell death and mass in syngenetically transplanted islets exposed to short- and long-term hyperglycemia
Diabetes
Superoxide-mediated activation of uncoupling protein 2 causes pancreatic β-cell dysfunction
J. Clin. Invest.
Uncoupling protein 2 and islet function
Diabetes
Functional and morphological alterations of mitochondria in pancreatic beta cells from type 2 diabetic patients
Diabetologia
Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes
Nat. Genet.
TCFL2: the biggest story in diabetes genetics since HLA?
Diabetologia
Common single nucleotide polymorphisms in TCF7L2 are reproducibly associated with type 2 diabetes and reduce the insulin response to glucose in nondiabetic individuals
Diabetes
Fetal and infant growth and impaired glucose tolerance at age 64
BMJ
In utero undernutrition impairs rat beta-cell development
Diabetologia
The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus
J. Clin. Invest.
The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes
Diabetologia
Reduced pancreatic β-cell compensation to the insulin resistance of aging: impact on pro-insulin and insulin levels
J. Clin. Endocrinol. Metab.
Role of reduced suppression of glucose production and diminished early insulin release in impaired glucose tolerance
N. Engl. J. Med.
Pancreatic beta-cell dysfunction as the primary genetic lesion of NIDDM
JAMA
Insulin resistance versus impaired insulin secretion as the genetic basis for type II diabetes
Curr. Opin. Endocrinol. Diab.
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