Three-year mortality in diabetic patients treated with different combinations of insulin secretagogues and metformin

BACKGROUND: Several studies have shown an increase of mortality in diabetic patients treated with combinations of sulphonylureas and biguanides. Comparisons between different insulin secretagogues in combination with metformin with respect to all-cause mortality have not been reported so far. METHODS: An observational cohort study was performed on a consecutive series of 2002 outpatients with type 2 diabetes mellitus. Of these patients, 696 (34.8%) were receiving combinations of insulin secretagogues and biguanides at enrollment. Three-year mortality was assessed through research in the City of Florence Registry Office. RESULTS: During follow-up, 295 deaths were recorded. Among patients on combined secretagogue and biguanide treatment, glibenclamide was associated with a significantly higher yearly mortality (8.7%) than repaglinide (3.1%; p = 0.002), gliclazide (2.1%; p = 0.001), and glimepiride (0.4%; p < 0.0001). After adjusting for potential confounders (including age; duration of diabetes; Body Mass Index (BMI); lipid profile; HbA(1c); insulin treatment; metformin doses; Charlson co-morbidity score; CCS), mortality remained significantly higher in patients treated with combinations of glibenclamide and metformin when compared to those treated with different insulin secretagogues (OR with 95% CI: 2.09 [1.07;4.11]). CONCLUSIONS: In the present study, sulphonylureas with greater selectivity for beta-cell receptors, such as glimepiride and gliclazide, were associated with a lower mortality when used in combination with metformin in comparison with glibenclamide. Safety of such combinations deserves further investigation.     

Comparison of acarbose and metformin in patients with Type 2 diabetes mellitus insufficiently controlled with diet and sulphonylureas: a randomized, placebo-controlled study.

AIMS: To compare the efficacy and safety of acarbose and metformin when added to sulphonylurea therapy in diabetic patients insufficiently controlled with sulphonylureas alone. METHODS: A 12-week, single-centre, placebo-controlled study, with 89 patients randomized to receive acarbose (100 mg t.d.s.), metformin (850 mg b.d.) or placebo in addition to their sulphonylurea therapy. The study was double-blinded with respect to acarbose/placebo and single-blinded for metformin/ acarbose and metformin/placebo. Patients started a strict dietary regimen 1 week before receiving their first dose of acarbose, metformin or placebo. This regimen was individually adjusted to metabolic status and energy requirements. RESULTS: The primary endpoint, HbA1c, decreased from baseline in all three groups after 12 weeks. The decrease was greater in the two groups receiving active therapy compared with placebo (acarbose -2.3+/-0.32%; metformin -2.5+/-0.16%; placebo -1.3+/-0.34%). There was no significant difference between acarbose and metformin (P=0.65). Differences between both active therapies and placebo were statistically significant (acarbose P < or = 0.01; metformin P < or = 0.004). Reductions in body weight over the treatment period were seen in all three groups and were greatest in the acarbose group (median weight reduction: acarbose 3.5 kg; metformin, 1.0 kg; placebo 1.4 kg). There were no significant differences in the incidence of gastrointestinal side-effects between the three groups and all regimens were generally well tolerated. CONCLUSION: The results of the study demonstrate the equivalence of acarbose and metformin for improving metabolic control in patients insufficiently controlled with diet and sulphonylureas.     

Metformin and reduced risk of hepatocellular carcinoma in diabetic patients with chronic liver disease

Background: Previous studies have reported the association between type 2 diabetes mellitus (DM2) and hepatocellular carcinoma (HCC). Aims: To explore the relationships among DM2, antidiabetic therapy and HCC risk. Methods: We recruited 610 HCC patients compared with 618 matched cirrhotic patients and 1696 Controls. The odds ratio (OR) for HCC in diabetic subjects treated with insulin, sulphonylureas and metformin was calculated. Results: DM2 prevalence was 31.2% in HCC, 23.3% in cirrhotic patients and 12.7% in Controls (P<0.0001). The OR for HCC in diabetic HCC patients vs Controls was 3.12 [confidence interval (CI) 2.40–3.90; P<0.001] in univariate analysis and 2.50 (CI 1.70–3.69; P<0.0001) in multivariate analysis. Comparing diabetic HCC patients vs liver cirrhosis (LC) cases, univariate analysis showed an OR for HCC of 2.09 (CI 1.50–2.90; P<0.001), whereas on multivariate analysis we found an OR of 1.46 (CI 1.07–1.98; P=0.02). In 84% of the cases, type 2 diabetes mellitus has been present before the HCC diagnosis. Multivariate analysis showed that metformin treatment was associated with a strong and statistically significant reduction of the risk of HCC, as compared with the use of sulphonylureas or insulin, in diabetic HCC patients vs Controls and vs LC cases (OR of 0.15; CI 0.04–0.50; P=0.005 and OR=0.16; CI 0.06–0.46; P=0.0006 respectively). Conclusions: Our study shows that DM2 is an independent risk factor for HCC and pre‐exists to HCC occurrence. In DM2 patients with HCC, metformin therapy is associated with a reduced HCC risk and seems to have a protective effect on HCC development.     

Mortality risk with sulphonylureas compared to metformin

Current clinical guidelines in the USA and the UK recommend first‐line glucose‐lowering treatment with metformin monotherapy for glucose control in type 2 diabetes, where not contraindicated. Consequently, the proportion of people treated with sulphonylureas is decreasing. The purpose of this commentary is to discuss the risks and benefits associated with sulphonylurea monotherapy versus metformin monotherapy and the evidence that, in comparison with metformin, sulphonylureas cause increased harm to people with type 2 diabetes.     

Metformin associated with lower mortality in diabetic patients with early stage hepatocellular carcinoma after radiofrequency ablation

Background and Aim: Type 2 diabetes increases the risk of cancer development and mortality. However, antidiabetic treatment with metformin can reduce the risk of cancer. We studied whether metformin users among diabetic patients with early hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA) would have a favorable survival compared with those without metformin treatment. Methods: A total of 135 patients with early stage HCC having 162 tumors underwent RFA. Among them, 53 patients were diabetic, including 21 metformin users and 32 patients without metformin treatment. Results: Diabetic patients had an inferior survival rate compared with nondiabetic patients (1 year, 82.8% vs 93.9%; 3 years, 55.1% vs 80.2%; 5 years, 41.3% vs 64.7%; P = 0.004). With regards to antidiabetic treatments, metformin users had better survival outcome (adjusted hazard ratio [HR] 0.24; 95% confidence interval [CI], 0.07–0.80; P = 0.020) compared to patients without metformin treatment after adjustments for potential confounders. Sulfonylureas and insulin exposures did not achieve significant conclusions. For the whole studied population including nondiabetic and diabetic patients, the multivariate analysis revealed that maximum tumor size more than 2.5 cm (HR, 3.49; 95% CI, 1.74–6.99; P < 0.001) and diabetic patients without metformin treatment (HR, 3.34; 95% CI, 1.67–6.71, P = 0.001) were independent explanatory variables associated with unfavorable survival. Conclusions: Metformin users among diabetic patients with HCC undergoing RFA had a favorable overall survival compared with patients without metformin treatment.     

二甲双胍对乳腺癌合并2型糖尿病患者癌组织Caspase-3、Caspase-9表达的影响

目的 观察二甲双胍对乳腺癌合并2型糖尿病患者癌组织中半胱天冬氨酸蛋白酶-3（Caspase-3）及Caspase-9表达的影响.方法 选择乳腺癌合并2型糖尿病112例,其中应用二甲双胍治疗者43例（二甲双胍组）、未用二甲双胍治疗者69例（糖癌组）,单纯乳腺癌112例（单纯癌症组）,采用免疫组化SP法检测癌组织中的Caspase-3、Caspase-9.结果 二甲双胍组癌组织中Caspase-3、Caspase-9表达量分别为138.24±8.68、140.21±6.34,糖癌组分别为153.43±5.59、156.17±8.25,单纯癌症组分别为112.70±4.28、121.43±6.67;三组两两比较,P均＜0.05.结论 二甲双胍可降低乳腺癌合并2型糖尿病患者癌组织中Caspase-3及Caspase-9表达,这可能是其抑制乳腺癌发展的作用机制.     

Effect of erythromycin on gallbladder emptying in diabetic patients with and without autonomic neuropathy and high levels of motilin

A reduction of gallbladder emptying in response to neural or hormonal stimulation has been reported in patients with diabetes mellitus. Decreased gallbladder emptying may be a key factor in the pathogenesis of gallbladder stones. Few drugs, if any, are able to stimulate gallbladder emptying. However, in a previous study we demonstrated that erythromycin, a macrolide antibiotic, stimulates gallbladder emptying and motilin release in healthy human subjects by an atropine-sensitive pathway. Therefore, the present study was designed to evaluate the effect of erythromycin on gallbladder emptying and motilin release in diabetic patients with or without cardiac autonomic neuropathy (AN). Thirteen diabetic patients, six with AN, and 10 healthy subjects were enrolled in the study protocol. Gallbladder emptying was determined by sonography after ingestion of a standard meal and during infusion of erythromycin alone or together with 6 g/kg/hr atropine. We found that 100 mg/hr erythromycin caused a significant reduction in gallbladder volume in both healthy subjects and diabetic patients. The ejection fraction (mean ±se) of 45.3±8.2% and 37.3±5.0% was similar. The presence of AN had no influence on gallbladder emptying induced by erythromycin. Basal motilin plasma levels were 111.5±14.5 pmol/liter in diabetic patients and 63.3 ±6.0 pmol/liter in healthy subjects (P<0.01). However, patients with AN had higher (130.0 ±11.9 pmol/liter) motilin plasma levels than patients without (74.0±9.4 pmol/liter,P<0.01). Erythromycin administration caused an approximately twofold increase in plasma motilin concentrations in healthy subject and patients withou AN, but did not stimulate motilin release in neuropathic patients. A negative correlation (r=–0.75,P<0.01) was found between basal plasma levels of motilin and peak of gallbladder emptying induced by erythromycin. Atropine completely inhibited the effects of erythromycin on gallbladder emptying and motilin release (P<0.001 by ANOVA). A negative correlation (r=–0.52,P<0.05) was also found between plasma glucose concentrations and peak of gallbladder emptying. Present results demonstrate that erythromycin could be used for treating alterations of gallbladder emptying in diabetic patients with or without AN.     

Differential effect of glimepiride and rosiglitazone on metabolic control of type 2 diabetic patients treated with metformin: a randomized, double-blind, clinical trial

AIM: Accumulating evidence suggests that combination therapy using oral antidiabetic agents with different mechanisms of action may be highly effective in achieving and maintaining target blood glucose levels. The aim of our study is to evaluate the differential effect on glucose and lipid parameters of the association between glimepiride plus metformin and rosiglitazone plus metformin in patients affected by type 2 diabetes and metabolic syndrome. METHODS: Patients were enroled, evaluated and followed at two Italian centres. We evaluated 99 type 2 diabetic patients with metabolic syndrome (48 males and 47 females; 23 males and 24 females, aged 52 +/- 5 with glimepiride; 25 males and 23 females, aged 54 +/- 4 with cglitazone). All were required to have been diagnosed as being diabetic for at least 6 months and did not have glycaemic control with diet and oral hypoglycaemic agents such as sulphonylureas or metformin, both to the maximum tolerated dose. All patients took a fixed dose of metformin, 1500 mg/day. We administered glimepiride (2 mg/day) or rosiglitazone (4 mg/day) in a randomized, controlled, double-blind clinical study. We evaluated body mass index (BMI), glycaemic control, lipid profile [total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol and triglycerides] and lipoprotein parameters [apolipoprotein A-I and apolipoprotein B (Apo B)] during 12 months of this treatment. RESULTS: A total of 95 patients completed the study. Significant BMI decrease was observed at 12 months in glimepiride and rosiglitazone group (p < 0.05 and p < 0.01 respectively) as well as of glycated haemoglobin decrease (p < 0.05 and p < 0.01 respectively), mean fasting plasma glucose and postprandial plasma glucose levels (p < 0.05 and p < 0.01 respectively). A decrease in fasting plasma insulin and postprandial plasma insulin at 12 months (p < 0.05 and p < 0.01 respectively) compared with the baseline value in rosiglitazone group was observed. Furthermore, homeostasis model assessment index improvement was obtained only at 9 and 12 months (p < 0.05 and p < 0.01 respectively) compared with the baseline value in rosiglitazone group. Significant TC, LDL-C and Apo B improvement (p < 0.05 respectively) was present in glimepiride group after 12 months compared with the baseline values, and these variations were significant (p < 0.05) between groups. Of the 95 patients who completed the study, 8.5% of patients in glimepiride group and 12.5% of patients in rosiglitazone group had side-effects (p = not significant). Four patients had transient side-effects in glimepiride group and six patients in rosiglitazone group. Altogether, we did not have statistically significant changes in transaminases. CONCLUSIONS: The rosiglitazone-metformin association significantly improve the long-term control of all insulin-resistance-related parameters in comparison with the glimepiride-metformin-treated group. On the other side, glimepiride treatment is associated to a slight improvement in cholesterolaemia, not observed in the rosiglitazone-treated patients.     

Cholecystokinin and pancreatic polypeptide release in diabetic patients with and without autonomic neuropathy

The present study was undertaken to investigate postprandial responses of cholecystokinin (CCK) and pancreatic polypeptide (PP) and their interrelationship in patients with diabetes mellitus (DM) with and without autonomic neuropathy (AN). Twenty-two patients with DM (seven with AN and 15 without AN) and 14 age-matched healthy controls were studied. AN was diagnosed according to several tests of cardiovascular autonomic function. CCK and PP plasma levels were measured by specific radioimmunoassays before and at several time points after the oral administration of a test meal. Basal CCK plasma levels in DM patients were normal, whereas basal PP plasma levels were increased (139±18 vs 72±7 pg/ml;P<0.01). integrated=" postprandial=" cck=" response=" was=" increased=" in=" dm=" patients=" (208±27=" vs=" 110±14=" pmol/liter/2=">P<0.05), mainly=" due=" to=" the=" patients=" with=" an.=" postprandial=" pp=" response=" was=" increased=" in=" dm=" patients=" without=" an=" (37,273±5241=" vs=" 13,418±3299=" pg/ml/2=">P<0.001) but=" not=" in=" those=" with=" an=" (8887±3461=" pg/ml/2=" hr).=" moreover,=" pp=" response=" was=" closely=">P<0.002) correlated=" with=" the=" degree=" of=" an.=" a=" direct=" and=" linear=" correlation=" between=" postprandial=" cck=" and=" pp=" responses=" was=" found=" in=" healthy=" controls=">r=0.78;P<0.005) but=" not=" in=" dm=" patients.=" we=" conclude=" that=" the=" cck=" response=" to=" a=" meal=" is=" increased=" in=" diabetic=" patients=" with=" an,=" whereas=" the=" pp=" response=" is=" increased=" only=" with=" an=" intact=" autonomic=" nervous=" system.=" it=" is=" suggested=" that=" the=" correlation=" between=" postprandial=" hormonal=" responses=" in=" healthy=" subjects=" is=" due=" to=" the=" potency=" of=" cck=" as=" pp=" releasing=" agent=" and=" that=" this=" interaction=" does=" not=" work=" in=" diabetic=">     

Lipoprotein risk factors for cardiovascular disease in patients with type 2 diabetes mellitus treated with oral antihyperglycaemic agents

Aims:  To compare lipoprotein risk factors for cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (DM) treated with a sulphonylurea (SU) compound only, metformin (MET) only, or combined SU + MET.
Methods:  The study population consisted of 62 patients with type 2 DM, whose antihyperglycaemic treatment program had been stable for at least 3 months, divided into three groups: 26 patients in the SU group, 17 patients in the MET group and 19 patients in the SU + MET group. None of the patients were taking lipid-lowering drugs. Fasting venous blood samples were taken to measure concentrations of glucose, total cholesterol, triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) and remnant lipoprotein-cholesterol (RLP-C) as well as for determination of LDL particle diameter.
Results:  The three groups were similar in terms of age, gender, body mass index and fasting plasma glucose concentrations. Total cholesterol concentrations were significantly lower (p < 0.05 for trend) in those treated with SU + MET as compared with the other two groups. However, there were no significant differences between the three groups in their plasma concentrations of TG, LDL-C, HDL-C or RLP-C; furthermore, the proportion of individuals within each treatment group with small LDL particle diameter was also not different.
Conclusions:  The lipoprotein profile of patients with type 2 DM, matched for level of fasting hyperglycaemia, was similar irrespective of treatment with SU alone, MET alone or SU + MET. Thus, we could not identify any changes in lipoprotein metabolism that could account for differences in risk of CVD as a function of treatment.     

Blood glucose may condition factor VII levels in diabetic and normal subjects

Summary Increased factor VII levels have been reported in Type 1 (insulin-dependent) diabetic subjects. A direct correlation between fasting plasma glucose and factor VII level was found to exist in both diabetic and normal subjects. Induced-hyperglycaemia was able to increase factor VII levels in both diabetic patients and normal control subjects while, when euglycaemia was achieved in diabetic patients, factor VII values returned to normal range. This study shows that the level of factor VII may be directly conditioned by circulating blood glucose and, therefore, stresses the role of hyperglycaemia in conditioning coagulation abnormalities in diabetes mellitus.     

Autonomic nervous function and its relationship to cardiac performance in middle-aged diabetic patients without clinically evident cardiovascular disease.

Autonomic nervous function was evaluated in 36 patients with insulin-dependent diabetes mellitus (IDDM), 39 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 48 control subjects, all without clinically evident cardiovascular disease. Valsalva ratio and heart rate variation during deep breathing were lower in both diabetic groups than in the control group. Autonomic nervous function score (ANFS) was more abnormal in patients with IDDM than in control subjects, but was not significantly increased in patients with NIDDM. There was a negative correlation between ANFS and left ventricular diastolic filling evaluated by echocardiography or peak heart rate during exercise in both diabetic groups. There were no correlations between ANFS and left ventricular systolic function at rest or during exercise in any of the groups. In conclusion, autonomic nervous function was abnormal in middle-aged diabetic patients, and it was associated with impaired left ventricular diastolic filling at rest and decreased heart rate response to exercise, but not with left ventricular systolic function.     

Albumin excretion rate levels in non-diabetic offspring of NIDDM patients with and without nephropathy

Summary Familial clustering of diabetic nephropathy points to genetic susceptibility. The observation that in non-diabetic subjects microalbuminuria occurs more frequently in the presence of a parental history of diabetes supports this hypothesis. However, the role of inherited factors is poorly understood in non-insulin dependent diabetes mellitus (NIDDM). This study investigated the albumin excretion rate in non-diabetic offspring of NIDDM patients with increased albumin excretion rate (>20 g/min) or normal albumin excretion rate (<20 g/min). We recruited 20 offspring of NIDDM patients with increased albumin excretion rate (A-off) and 20 offspring of NIDDM patients with normal albumin excretion rate (N-off), matched for age, sex, body mass index, blood pressure and estimated protein intake. All offspring were normotensive, had normal creatinine clearance, normal glucose tolerance and sterile urine collection. Albumin excretion rate was measured on three sterile overnight urine collections and median values were used for calculations. Albumin excretion rate was significantly higher in A-off than in N-off (7.7±1.2 vs 3.4±0.6 g/min p<0.01) and significantly related to parents' albumin excretion rate (p<0.01, r=0.53). These results suggest that an increased glomerular permeability is present in non-diabetic offspring of NIDDM patients with increased albumin excretion rate.Abbreviations NIDDM Non-insulin-dependent diabetes mellitus - AER albumin excretion rate - OGTT oral glucose tolerance test - A-off offspring of NIDDM patients with increased albumin excretion rate - N-off offspring of NIDDM patients without increased albumin excretion rate     

不同病程2型糖尿病患者皮质醇水平及其影响因素分析

目的 探讨2型糖尿病患者皮质醇（Cor）水平变化及其影响因素.方法 将98例2型糖尿病患者作为病例组,按病程分为3个亚组：病程＜5年组,病程5-15年组,病程≥15年组;以体检的健康人群98例作为正常对照组.测定受试对象的晨8时血促肾上腺皮质激素（ACTH）、血皮质醇（Cor）、24小时尿游离皮质醇（UFC）等.结果 （1）在2型糖尿病组血ACTH、Cor、UFC水平均高于正常对照组,差异有统计学意义（P＜0.01）;（2）2型糖尿病患者血ACTH、Cor、UFC平均水平随糖尿病病程的延长而升高,但在3个亚组间血ACTH、Cor比较差异无统计学意义,UFC于病程≥15年组与病程＜5年组间比较差异有统计学意义（P＜0.01）;（3）多元逐步回归分析显示2型糖尿病患者血ACTH与糖尿病慢性并发症数目呈正相关,与年龄呈负相关（P＜0.01）;Cor与慢性并发症数目、HbAlc呈正相关（P＜0.01）,与性别呈负相关（P＜0.05）;UFC与病程、WHR呈正相关、与性别呈负相关（P＜0.01）.结论 （1）2型糖尿病患者血ACTH、Cor、UFC水平较正常人群明显升高.（2）2型糖尿病患者皮质醇的分泌与糖尿病病程、慢性并发症数目、年龄、性别、腰臀比及糖代谢水平相关.     

Systemic resistin is increased in type 2 diabetic patients treated with loop diuretics

Increased serum resistin was found in rodent models of obesity and insulin resistance, whereas contradictory results have been obtained in human studies. In humans, resistin is primarily released by monocytes/macrophages, suggesting that soluble levels may be associated with macrophage activation. Here, systemic and monocyte-released resistin levels were found to be similar in type 2 diabetic (T2D) patients, overweight controls and normal-weight controls. When adjusted for body mass index and age, serum resistin modestly correlated with gamma-glutamyltransferase levels, fasting glucose and interleukin-6. Systemic resistin was marginally increased in T2D patients treated with beta-blockers or urate-lowering drugs and was considerably higher in patients treated with loop diuretics. Monocyte-released resistin was even reduced by the loop diuretic furosemide, excluding the possibility that this drug may directly stimulate resistin synthesis. In summary, the current data indicate that changes accompanying renal dysfunction but not obesity or type 2 diabetes are associated with increased serum resistin.     

Cancer mortality reduction and metformin: a retrospective cohort study in type 2 diabetic patients

Aims: Few studies suggest that metformin decreases cancer mortality in type‐2 diabetic patients (T2DP). We explored the association between the type and duration of antidiabetic therapies and cancer and other‐than‐cancer mortality in a T2DP cohort, taking into account the competing risks between different causes of death and multiple potential confounding effects. The mortality rates were compared with the general population from the same area. Methods: In 1995, all T2DP (n = 3685) at our diabetes clinic in Turin (～12% of all T2DP in the city), without cancer at baseline, were identified. Vital status was assessed after a mean 4.5‐year follow‐up. Results: Metformin users had greater adiposity, while insulin users had more co‐morbidities. All‐cause‐ and cancer‐related deaths occurred in: 9.2 and 1.6% of metformin users, 13.1 and 3.0% of sulfonylureas users and 26.8 and 4.8% of insulin users, respectively. In a Cox regression model for competing risks, adjusted for propensity score, metformin users showed a lower cancer mortality risk [hazard ratio (HR) = 0.56; 95% confidence interval (CI) 0.34–0.94], while insulin was positively associated with other‐than‐cancer mortality (HR = 1.56; 95%CI 1.22–1.99). Each 5‐year metformin exposure was associated with a reduction in cancer death by 0.73, whereas every 5‐year insulin exposure was associated with 1.25‐fold increase in other‐than‐cancer death. Standardized mortality ratios for cancer and other‐than‐cancer mortality in metformin users were 43.6 (95%CI 25.8–69.0) and 99.1 (95%CI 79.3–122.5), respectively, in comparison with the general population. Conclusions: Metformin users showed a lower risk of cancer‐related mortality than not users or patients on diet only; this may represent another reason to choose metformin as a first‐line therapy in T2DP.     

Leptin levels in diabetic and nondiabetic subjects

The role of leptin in human pathophysiology elicits considerable interest in view of its potential role as a treatment tool for obesity and other insulin resistant states, like type 2 diabetes mellitus (T2DM). Leptin has been extensively studied in obese humans, and much less so in other pathologic conditions. Leptin level has been reported to correlate with percent body fat mass (%FM), fasting serum insulin (FPI), insulin sensitivity and blood pressure. The aim of this study was to compare the leptin concentration, and its relationship with some anthropometric and biochemical parameters related to insulin resistance in 140 moderately obese type 2 diabetics (T2DM) and 160 age and weight matched non-diabetic controls in order to get a better insight into the possible role of leptin in the metabolic abnormalities of diabetes. The leptin levels were lower in the diabetic population only when both sexes were combined (p<0.05) and were higher in the females of both groups. Among the nondiabetics, the leptin levels appeared to be related to BMI, %FM, HDL and FPI, while this was not the case in the diabetics. After correction for BMI, leptin appeared to be correlated with the FPI levels only in the non-diabetic females. When plasma leptin was included in a multiple linear regression model with plasma leptin as a dependent variable, BMI, W:Hr and FPI levels were significantly related to leptin in the non diabetic population, while no relationship reached the level of statistical significance among the diabetics, with the exception of the borderline value for the FPI (p=.052). In conclusion, leptin levels were independent of any of the parameters examined in our diabetic population, possibly due to the progressive loss of the normal mechanisms of leptin regulation with advancing disease. Conclusive data can only be obtained from the longitudinal study of a cohort of newly diagnosed diabetic subjects.