Non-insulin-dependent (Type 2) Diabetes Mellitus Research Articles

Carriers of the TCF7L2 rs7903146, rs12255372 Risk Alleles in the South Tamil Nadu T2DM Patients Present with Early Incidence and Insulin Dependence.

Background and Aims:Metabolic abnormalities in T2DM (Type 2 diabetes mellitus) include classic manifestations such as impaired insulin secretion, synthesis and peripheral insulin resistance. The intronic variants rs7903146 and rs12255372 of the TCF7L2 (transcription factor 7-like 2) gene are strongly associated with risk of incidence of T2DM and impaired β-cell functions. Studies addressing the early T2DM onset, and early insulin dependence in T2DM patients of south Tamil Nadu are still lacking, and hence the present study focuses in determining the influence of the TCF7L2 polymorphisms in the incidence and disease course in the T2DM patients of south Tamil Nadu.Methods:Anthropometric measurements and biochemical parameters were carried out in early onset (Group A), early onset insulin dependent T2DM patients (Group B) and non-insulin dependent T2DM patients (Group C). PCR, allele specific PCR (ASP), PCR product sequencing strategies were utilized to determine the genotype and the impact of the TCF7L2 SNPs in the T2DM disease course.Results:Female T2DM patients with the CT/TT rs7903146 genotype (P = 0.005) and the rs12255372 GT/TT genotype (P = 0.036) exhibited a significantly low mean age for T2DM incidence. Correlation/regression analysis in the T2DM patients revealed that rs12255372 (P = 0.042) is associated with early onset in the Group C patients and the rs7903146 (P = 0.018), rs12255372 (P = 0.026) are associated with insulin dependence in the group B patients.Conclusion:Screening for the TCF7L2 polymorphisms will prevent T2DM incidence and enable life style changes, appropriate therapeutic strategies that would help combat the accelerated disease course in the T2DM patients.

Low dose resveratrol improves cerebrovascular function in type 2 diabetes mellitus

Background and aimsProgressive microvascular dysfunction in type 2 diabetes mellitus (T2DM) may impair the ability of cerebral vessels to supply blood to brain regions during local metabolic demand, thereby increasing risks of dementia. Having previously demonstrated that resveratrol can enhance vasodilator function in the systemic circulation, we hypothesised that resveratrol could similarly benefit the cerebral circulation. We aimed to determine the most efficacious dose of resveratrol to improve cerebral vasodilator responsiveness (CVR) in T2DM. Methods and resultsIn a double-blind, placebo-controlled, balanced crossover intervention, 36 dementia-free, non-insulin dependent T2DM older adults (49–78 years old) consumed single doses of synthetic trans-resveratrol (0, 75, 150, and 300 mg) at weekly intervals. Transcranial Doppler ultrasound was used to assess CVR to a hypercapnic stimulus, both before and 45 min after treatment. CVR, measured bilaterally in the middle cerebral arteries (MCA) and posterior cerebral arteries (PCA), was expressed as the percentage change in mean blood flow velocity from baseline to the peak velocity attained during hypercapnia. Resveratrol consumption increased CVR in the MCA; mean within-individual changes for each dose from placebo were 13.8 ± 3.5% for 75 mg (P = 0.001), 8.9 ± 3.5% for 150 mg (P = 0.016), and 13.7 ± 3.3% for 300 mg (P < 0.001); only the 75 mg dose was efficacious in the PCA (13.2 ± 4.5%, P = 0.016). ConclusionsOur results provide the first clinical evidence of an acute enhancement of vasodilator responsiveness in cerebral vessels following consumption of resveratrol in this population who are known to have endothelial dysfunction and sub-clinical cognitive impairment. Importantly, maximum improvement was observed with the lowest dose used. Clinical trial registrationACTRN12614000891628 (www.anzctr.org.au).

Effects of a 12-wk whole-body vibration based intervention to improve type 2 diabetes

ObjectiveTo test the feasibility, safety and effectiveness of a 12-wk whole body vibration (WBV) intervention on glycemic control, lipid-related cardiovascular risk factors and functional capacity among type 2 diabetes mellitus (T2DM) patients in a primary care context. MethodsFifty non-insulin dependent T2DM patients were randomized 1:1 to an intervention group that, in addition to standard care, received a 12-wk WBV intervention, and a control group receiving only standard care (from February 2012 through May 2012). Outcomes, including glycated hemoglobin (HbA1c), fasting blood glucose, lipid-related cardiovascular risk factors (i.e., cholesterol, triglycerides, lipoproteins, LDL/HDL and atherogenic index) and functional capacity were measured at baseline and after the 12-wk intervention. ResultsAfter intervention, there was a reduction in HbA1c and fasting blood glucose when compared to the control group, with a mean difference in change scores between groups of −0.55% (95% CI −0.15 to −0.76) and −33.95mm/dl (95% CI −51.38 to −3.47), respectively. Similarly, most lipid-related cardiovascular risk factors (i.e., cholesterol, triglycerides and atherogenic index) were also reduced (p<0.05). ConclusionA 12-wk WBV intervention in a primary care context is feasible, safe and effective in improving glycemic profile, lipid-related cardiovascular risk factors and functional capacity among T2DM patients. Trial numberACTRN12613000021774.

Activity of the Chinese prescription Hachimi-jio-gan against renal damage in the Otsuka Long-Evans Tokushima Fatty rat: a model of human type 2 diabetes mellitus

Currently, in Japan, approximately 95% of patients with diabetes mellitus have non-insulin-dependent (type 2) diabetes mellitus (NIDDM), and diabetic nephropathy is a major cause of patients requiring chronic haemodialysis. A previous study showed that Hachimi-jio-gan has a protective effect in rats subjected to subtotal nephrectomy plus streptozotocin injection, a model of insulin-dependent (type 1) diabetic nephropathy. In this study, we used the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of human NIDDM, to investigate whether long-term administration of Hachimi-jio-gan affects glycaemic control and renal function in NIDDM. Male OLETF rats, aged 22 weeks, were divided into 4 groups of 10 and given Hachimi-jio-gan (50, 100 or 200 mg kg(-1) daily) orally or no treatment for 32 weeks. Male Long-Evans Tokushima Otsuka (LETO) rats (n = 6) were used as non-diabetic normal controls. Hachimi-jio-gan reduced hyperglycaemia dose-dependently from 16 weeks of the administration period. Urinary protein excretion decreased significantly from an early stage, and creatinine clearance levels improved at 32 weeks. In addition, the levels of serum glycosylated protein and renal advanced glycation end-products were effectively reduced. Hachimi-jio-gan also significantly reduced the levels of thiobarbituric acid-reactive substances in renal mitochondria, although it showed only a tendency to reduce these in serum. Furthermore, long-term administration of Hachimi-jio-gan reduced renal cortical expression of proteins, such as transforming growth factor-beta1 (TGF-beta1), fibronectin, inducible nitric oxide synthase and cyclooxygenase-2. The 100- and 200-mg kg(-1) daily doses of Hachimi-jio-gan significantly reduced TGF-beta1 and fibronectin protein expression to levels below those of LETO rats. These data suggest that Hachimi-jio-gan may have a beneficial effect on the progression of diabetic nephropathy in OLETF rats by attenuating glucose toxicity and renal damage.

Glucose‐dependent insulinotropic polypeptide–producing K cells in dexamethasone‐treated rats

Some studies indicate that diabetes mellitus exerts an influence on the gastrointestinal tract and its diffuse neuroendocrine system (DNES) in regard to cellular density and neuroendocrine content. Since there is no data about relationship between experimentally induced non-insulin-dependent (type 2) diabetes mellitus (NIDDM) on the gut K cells, the aim of our study was to investigate immunohistochemical, stereological and ultrastructural changes of rat K cells after 12 days of dexamethasone treatment. Twenty male Wistar rats aged 30 days were given daily intraperitoneally 2 mg kg(-1) dexamethasone (group DEX, 10 rats) or saline (group C, 10 rats) for 12 days. Tissue specimens were obtained from each antrum with corpus and different parts of the small (SI) and large intestine (LI) of all animals. Immunohistochemistry was carried out using antisera against the GIP and insulin. Transmission electron microscopy was also used. Although, according to the literature data, rat K cells are present in the duodenum and jejunum and, to a lesser extent, in the ileum, in the present study we observed that those cells were abundant also in all parts of the LI. We observed generally that GIP-producing K cells were augmented in all parts of SI and decreased in the LI of DEX rats. Insulin immunoreactivity (ir) coexpressed with GIP-ir in K cells and was stronger in the SI of DEX rats as compared with C rats. We also found by electron microscopy that small intestinal K cells have features not only of GIP-secreted but also of insulin-secreted cells. We concluded that dexamethasone treatment caused proliferation of K cells in the rat SI, and simultaneously transformation of GIP-producing K cells to insulin-synthesizing cells.

Preoperative Oral Carbohydrate Administration to ASA III-IV Patients Undergoing Elective Cardiac Surgery

In this study we investigated the effects of preoperative oral carbohydrate administration on postoperative insulin resistance (PIR), gastric fluid volume, preoperative discomfort, and variables of organ dysfunction in ASA physical status III-IV patients undergoing elective cardiac surgery, including those with noninsulin-dependent Type-2 diabetes mellitus. Before surgery, 188 patients were randomized to receive a clear 12.5% carbohydrate drink (CHO), flavored water (placebo), or to fast overnight (control). CHO and placebo were treated in double-blind format and received 800 mL of the corresponding beverage in the evening and 400 mL 2 h before surgery. Patients were monitored from induction of general anesthesia until 24 h postoperatively. Exogenous insulin requirements to control blood glucose levels <or=10.0 mmol/L were used as a marker for PIR. Gastric fluid volume was measured by passive gastric reflux and preoperative discomfort using visual analog scales. Postoperative clinical and surgical data were recorded. Blood glucose levels and insulin requirements did not differ between groups. Patients receiving CHO and placebo were less thirsty compared with controls (P < 0.01 and P = 0.06, respectively). Ingested liquids did not cause increased gastric fluid volume or other adverse events. The CHO group required less intraoperative inotropic support after initiation of cardiopulmonary bypass weaning (P < 0.05). In conclusion, preoperative CHO administration before cardiac surgery does not affect PIR. Clear fluids reduce thirst and may be recommended as a safe procedure in ASA III-IV patients. Further research is indicated to investigate possible cardioprotective effects of preoperative CHO intake.

β-cell autoantibodies in children with type 2 diabetes mellitus: subgroup or misclassification?

Background: In adults, a fraction of diabetic individuals with β-cell autoantibodies has initially non-insulin requiring diabetes clinically appearing as type 2 diabetes mellitus (T2DM), named latent autoimmune diabetes in adulthood...

Thiols, malonaldehyde and total antioxidant status in the Turkish patients with type 2 diabetes mellitus.

Non-insulin dependent (Type 2) diabetes mellitus (NIDDM) is a risk factor for cardiovascular diseases (CVD). Oxidative stress mechanisms are often reported to be implied in type 2 diabetes mellitus. In order to determine their clinical relevance, we investigated several plasma indicators in the Turkish patients with NIDDM: (i) homocysteine (Hcy) and cysteine (Cys) which contribute to increase the risk of atherosclerosis during NIDDM, (ii) glutathione (GSH) and cysteinylglycine (CysGly) resulting from GSH degradation catalyzed by gamma-glutamylcysteine transferase (GGT), (iii) malonaldehyde (MDA) as a marker for lipid peroxidation, and (iv) total antioxidant status (TAS). Our main results were evaluated based on sex and diabetic status. In female patients, plasma concentrations of MDA and Hcy were significantly higher than in controls, while GSH levels were significantly lower. In males, a difference between control and diabetic groups was noticed only for Hcy, levels being also higher in patients. In the diabetic group, increase in serum glucose concentration was significantly correlated with increased GGT activity. In both controls and diabetic patients, GGT activity was correlated with a raised Cys concentration and a decreased GSH level. In both controls and diabetic patients, there were significant positive correlations between Cys and Hcy and between GSH and Hcy. We concluded that GSH and MDA levels are clinical indicators for an oxidative process linked to type 2 diabetes mellitus, especially in women.

Dyslipoproteinaemia and hyperoxidative stress in the pathogenesis of endothelial dysfunction in non-insulin dependent diabetes mellitus: an hypothesis

Endothelial dysfunction in non-insulin dependent (Type 2) diabetes mellitus (NIDDM) has implications for the pathogenesis of the two major complications, macrovascular disease and microangiopathy. Endothelial dysfunction is a consequence of a disturbance in the l-arginine/nitric oxide pathway. Its occurrence in NIDDM is well supported by both in vitro and in vivo studies. NIDDM results in diverse abnormalities in lipoprotein metabolism, the most significant being hypertriglyceridaemia which is associated with increased plasma concentrations of small dense LDL and low levels of HDL. Dysglycaemia results in hyperoxidative stress and increased formation of advanced-glycosylation endproducts, both of which enhance the oxidative modification of lipoprotein particles. Based on extensive in vitro studies and on human data, we generate the hypothesis that the development of endothelial dysfunction in NIDDM is a consequence of the effect of dyslipoproteinaemia, in particular increased circulatory concentrations of modified small dense LDL and of hyperoxidative stress on the formation, action and disposal of nitric oxide, by diverse molecular mechanisms; HDL is proposed to have a protective effect on these processes through its enzymic antioxidant properties. The hypothesis proposed is simple, testable and consistent with wide sources of evidence. The practical implications of the hypothesis and the existing opportunities for the prevention and reversal of endothelial dysfunction in NIDDM are also reviewed and discussed.

Low-density lipoprotein size, high-density lipoprotein concentration, and endothelial dysfunction in non-insulin-dependent diabetes.

We examined endothelial function (nitric-oxide mediated) in 29 men with diet-treated non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) and 18 male age-matched controls. Forearm blood flow was measured by venous occlusive plethysmography during intra-arterial administration of acetylcholine (ACh, 7.5 and 15 microg min(-1)) and sodium nitroprusside (SNP, 3 and 10 microg min(-1)). LDL particle size was estimated by non-denaturing gel electrophoresis. Serum lipids, blood pressure, and glycated haemoglobin were also measured. LDL particle size was smaller (p = 0.048) in the diabetic patients than controls. In the diabetic patients, LDL particle size was a significant positive predictor (p = 0.01) of the area under the dose-response curve for ACh, after adjusting for age, HbA1c, systolic BP, and cholesterol (R2 0.20). In stepwise regression including serum lipid and lipoprotein concentrations and LDL particle size, decreased HDL cholesterol was the best predictor of an impaired vasodilatory response to ACh. Vasodilatory responses to sodium nitroprusside were not significantly correlated with LDL particle size or serum lipid and lipoprotein concentrations. We conclude that in men with NIDDM, small, dense LDL particle size is associated with abnormal endogenous release of nitric oxide. The contribution of small, dense LDL particles to the development of endothelial dysfunction and early diabetic vasculopathy may not, however, be as great as decreased HDL cholesterol.

Divergent association of apolipoprotein E polymorphism with vascular disease in patients with NIDDM and control subjects

We analysed a well-characterized group of 83 patients (43 men, 40 women; mean age ± SEM: 65.5 ± 0.6 years at the 10-year examination) with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) and in 123 control subjects (56 men, 67 women; mean age ± 0.9 years) retrospectively for the relationship of apolipoprotein E (apo E) genotypes (E2/3, E3/3 vs E3/4, E4/4) to the incidence of clinical macrovascular disease and its risk factors and the incidence of microvascular complications of diabetes during the first 10 years of NIDDM, as well as carotid intima-media thickness measured by B-mode ultrasound at the 10-year examination. In patients with NIDDM, apo E4 genotype showed no relationship to clinical events or carotid intima-media thickness. However, in the control subjects with apo E4, the incidence of non-fatal myocardial infarction during the follow-up was increased (apo E4 positivity: 17.1 %; apo E4 negativity 5.1 %; p = 0.035) and they had higher common carotid intima-media thickness than those with apo E2/3 or apo E3/3 (1.15 ± 0.05 mm vs 1.01 ± 0.03 mm, p = 0.008). Apo E genotype groups showed no relationship to microvascular complications of diabetes, although control subjects with apo E4 positivity showed a higher frequency of microalbuminuria than those lacking apo E4. We conclude that apo E4 was a marker of vascular disease and increased atherosclerosis in non-diabetic subjects, whereas in the diabetic patients these relationships were absent. It is likely that NIDDM per se influences the vascular risk so overwhelmingly that the effects of other risk factors are obscured. © 1997 by John Wiley & Sons, Ltd.

Patient awareness of genetic and environmental risk factors in non-insulin-dependent diabetes mellitus--relevance to first-degree relatives.

Primary preventative strategies may be useful in non-insulin-dependent (Type 2) diabetes mellitus (NIDDM), where weight reduction and physical exercise may help to counteract the increased risk to first-degree relatives of affected patients. To assess the extent of patient's awareness of these and related issues, 100 NIDDM patients were selected to complete a questionnaire. Forty-four per cent had a family history of NIDDM. Forty per cent and 35%, respectively, were aware that the patient's siblings and children were at an increased risk of developing NIDDM. Sixty-three per cent and 35%, respectively, were aware that obesity and physical inactivity increased the risk of developing NIDDM. After appropriate counselling about these risk factors, all 100 patients claimed that they would be advising their first-degree relatives. However, at 4 months review, 53% of patients had informed their first-degree relatives of the increased genetic risk to them. Of these patients, 83%, 74%, and 23% had provided relevant advice on diet, weight reduction, and physical exercise, respectively, as a means of reducing the risk of first-degree relatives developing NIDDM. We conclude that only a small proportion of patients are aware of the increased genetic susceptibility of their first-degree relatives to develop NIDDM and that weight reduction and regular physical exercise can reduce this risk. But, after appropriate education, a significant proportion of NIDDM patients did inform their close relatives of these issues and this may prove to be a useful strategy in the primary prevention of NIDDM.

Mortality in older people with diabetes mellitus.

It is universally acknowledged that diabetes mellitus is a common cause of morbidity in the elderly population but it is less well established that the mortality of people with diabetes is greater at any given age. This comprehensive literature review aims to examine the evidence in order to clarify the relationship between diabetes and mortality risk in elderly diabetic patients. Information was obtained by carrying out a MEDLINE search for relevant papers published in 1980 and onwards; a key paper on mortality in non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) was used as an index paper; Diabetes, Diabetologia, Diabetic Medicine, Diabete et Metabolisme, and Diabetes Care were hand searched; and, finally, other experts in the field were contacted. Two reviewers independently extracted the data from each of the studies and disagreements were discussed and resolved. The studies in elderly study populations comprised mainly NIDDM. The review demonstrated that diabetes is a significant contributor to mortality and reduced life expectancy in elderly subjects. Demographic trends in our population indicate that diabetes will continue to be a challenging health problem.

Community‐based Approaches for the Primary Prevention of Non‐insulin‐dependent Diabetes Mellitus

The prevalence of non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) is increasing worldwide. Although recent studies suggest that primary prevention of NIDDM is possible, strategies for controlling the NIDDM pandemic remain under development. Successful interventions to date have mainly relied upon the control of obesity and increased exercise, although pharmacological agents are being studied. While a mixture of both high risk and population-based approaches is likely to be required, the former will not prevent new high risk cases developing. Unfortunately, the success in the primary prevention of cardiovascular disease through risk factor reduction has not controlled obesity, the most important risk factor for NIDDM. New strategies are currently being developed and focus upon changes in the food supply of whole populations and a community development approach to altering attitudes to food and exercise. As these interventions are in the early stages of their development, formative, process, and quantitative evaluation remain essential components of any community-based programme aimed at the primary prevention of NIDDM. © 1997 John Wiley & Sons, Ltd.

Community-based approaches for the primary prevention of non-insulin-dependent diabetes mellitus.

The prevalence of non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) is increasing worldwide. Although recent studies suggest that primary prevention of NIDDM is possible, strategies for controlling the NIDDM pandemic remain under development. Successful interventions to date have mainly relied upon the control of obesity and increased exercise, although pharmacological agents are being studied. While a mixture of both high risk and population-based approaches is likely to be required, the former will not prevent new high risk cases developing. Unfortunately, the success in the primary prevention of cardiovascular disease through risk factor reduction has not controlled obesity, the most important risk factor for NIDDM. New strategies are currently being developed and focus upon changes in the food supply of whole populations and a community development approach to altering attitudes to food and exercise. As these interventions are in the early stages of their development, formative, process, and quantitative evaluation remain essential components of any community-based programme aimed at the primary prevention of NIDDM.

Nisoldipine blocks the increase of intracellular free calcium-ion concentration associated with elevated sodium-lithium countertransport activity in erythrocytes in patients with NIDDM.

To understand the mechanism by which elevated sodium-lithium countertransport activity (SLC) associates with increased intracellular free calcium-ion concentration ([Ca2+]i), we investigated the relationship between SLC and the effects of the extracellular Ca2+ concentration ([Ca2+]o) and a Ca2(+)-channel blocker, nisoldipine, on [Ca2+]i in erythrocytes from 48 patients with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM). There was a significant correlation between SLC and [Ca2+]i. Nisoldipine in the incubation medium significantly decreased [Ca2+]i, and there was a significant positive correlation between SLC and the degree of [Ca2+]i decrease. When the [Ca2+]o was elevated, [Ca2+]i was significantly increased, but nisoldipine almost completely suppressed this increase of [Ca2+]i. There was a significant positive correlation between SLC and the degree of the suppression. These data suggest that elevated SLC correlates with increased [Ca2+]i, and that the increased [Ca2i]i might be due to the increased Ca2+ influx through a dihydropyridine-sensitive Ca2+ pathway.

Diabetic retinopathy assessed by fundus photography in Pima Indians with impaired glucose tolerance and NIDDM

In a population-based epidemiological study, 991 Pima Indians with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) and 288 without diabetes aged > or =15 years were examined for retinopathy by fundus photography with a 45 degrees fundus camera after mydriasis. The photographs were graded using a modified Airlie-House classification scheme. The associations of several factors with retinopathy were studied by logistic regression. Non-proliferative retinopathy was present in 11.2 % (19/169) subjects at the time of diagnosis of diabetes and in 8.3% (4/48) in newly diagnosed subjects who had a documented non-diabetic oral glucose tolerance test within 4 years prior to diagnosis of diabetes. The prevalence of retinopathy in subjects with impaired glucose tolerance was 12% (8/68). Retinopathy at the time of diagnosis of diabetes was significantly associated with lower body mass index and higher systolic blood pressure but not glycaemia. Retinopathy was present in 375 (37.8 %) diabetic subjects and 14 (5.2 %) non-diabetic subjects. Among all subjects with diabetes (duration 0-37 years), stepwise multivariate analysis showed non-proliferative retinopathy to be associated with duration of diabetes, mean blood pressure, fasting plasma glucose, treatment with insulin and albuminuria. Proliferative retinopathy was seen in 34 (2.7%) of diabetic and none of the non-diabetic subjects, and was associated with 2 h post-load glucose concentrations, as well as albuminuria, insulin treatment, younger age, and diastolic blood pressure. These data confirm the need for fundus examination at the time of diagnosis of diabetes and during long-term follow-up. Albuminuria and blood pressure are potentially modifiable risk factors and the impact of treating these on incidence and progression of diabetic retinopathy need to be assessed.

Estimation of unascertained diabetes prevalence: different effects on calculation of complication rates and resource utilization.

The incidence and prevalence of insulin-dependent (Type 1) diabetes mellitus (IDDM) in populations are both well defined. In the more prevalent non-insulin-dependent (Type 2) diabetes mellitus (NIDDM), which is responsible for the bulk of diabetes-related morbidity, true prevalence is uncertain because of delayed diagnosis and problems of definition, particularly with increasing age. Estimates therefore vary widely. We have previously presented evidence of increased relative probability of hospital admission for people with diabetes. These absolute and relative rates of admission were based on a large scale community-derived prevalence for diabetes of 1.36%. Assuming that the true prevalence of diabetes is higher, recalculation of activity data in a sensitivity analysis suggests a theoretical maximum prevalence of diabetes of 5% in our population, since a higher value would imply less morbidity associated with diabetes than 'non-diabetes'. This approach identifies the possible range of unascertained diabetes in a population and defines it in functional terms as that state carrying any excess risk of admission for complications when compared to non-diabetes. Higher estimates of prevalence have little impact on the calculation of overall resource use for diabetes, since the great majority of costs are related to fixed hospital activity for people with identified diabetes. The unascertained diabetes sub-group will cost little by comparison. Paradoxically, the tendency to use higher estimates of unascertained diabetes increases the denominator for calculation of complication rates and reduces both the absolute and relative risk of complications. This dilutes the epidemiological significance of diabetes in the aetiology of its related complications.

Relationships Between Plasma Leptin and Insulin Concentrations, But Not Insulin Resistance, in Non-insulin-Dependent (Type 2) Diabetes Mellitus

In non-diabetic subjects, insulin concentrations and insulin resistance are clearly connected, and both correlate with leptin levels, making interpretations about mechanisms difficult. In non-insulin-dependent (Type 2) diabetes mellitus (NIDDM), however, insulin concentrations and insulin resistance are less closely associated. Therefore, we examined the relationship of plasma leptin concentrations within insulin resistance and insulin levels in 32 subjects with NIDDM, who underwent measurement of insulin resistance with an insulin sensitivity test. Plasma leptin was measured with an in-house monoclonal immunoradiometric assay. Fasting leptin level correlated with BMI (r = 0.78; p < 0.001), metabolic clearance rate of glucose (= -0.44; p = 0.015), and fasting specific insulin (r = 0.58; p = 0.001), but not with age, cholesterol, triglycerides or blood pressure (r = -0.26 to 0.21; p = NS). In linear regression analysis, after adjustment for BMI and gender, leptin concentrations correlated with those of insulin (partial r = 0.42; p = 0.025), but not insulin resistance (partial r = -0.10; p = NS). We conclude that in NIDDM, concentrations of plasma leptin are closely related to those of insulin per se and to obesity, but not to insulin resistance. Insulin may be an important regulator of leptin concentration in NIDDM.

The role of insulin resistance in the natural history of type 1 diabetes.

It is well established that peripheral insulin sensitivity is a critical factor in the aetiology of non-insulin dependent (Type 2) diabetes mellitus (NIDDM). Insulin resistance may also play a role at various stages in the natural history of insulin dependent (Type 1) diabetes (IDDM) and this was the topic of a workshop held in London on Friday 14 July 1995. The mechanisms of insulin resistance in IDDM are ill-defined but probably include 'glucose toxicity'. In the pre-diabetic period, insulin resistance may affect rates of progression to frank hyperglycaemia. Following the clinical onset of IDDM, insulin resistance could influence the length of the 'honeymoon period', diabetic control and patterns of growth during puberty, insulin requirements and blood glucose control at any time, the birth weight of infants born to diabetic mothers, and, through an effect on lipid metabolism and hypertension, ultimately contribute to the excess mortality associated with IDDM. In NIDDM, insulin resistance could influence rates of progression to insulin dependence. Treatment using insulin enhancers in NIDDM patients with autoimmune changes might delay or arrest their usual high-risk of progression to insulin dependence. As it is likely that insulin resistance has a wide-ranging influence on the natural history of diabetes in IDDM patients we suggest that treatment with insulin enhancers may prove beneficial in selected patients.