To determine the influence of dietary fructose and glucose on circulating leptin levels in lean and obese rats, plasma leptin concentrations were measured in ventromedial hypothalamic (VMH)-lesioned obese and sham-operated lean rats fed either normal chow or fructose- or glucose-enriched diets (60% by calories) for 2 wk. Insulin resistance was evaluated by the steady-state plasma glucose method and intravenous glucose tolerance test. In lean rats, glucose-enriched diet significantly increased plasma leptin with enlarged parametrial fat pad, whereas neither leptin nor fat-pad weight was altered by fructose. Two weeks after the lesions, the rats fed normal chow had marked greater body weight gain, enlarged fat pads, and higher insulin and leptin compared with sham-operated rats. Despite a marked adiposity and hyperinsulinemia, insulin resistance was not increased in VMH-lesioned rats. Fructose brought about substantial insulin resistance and hyperinsulinemia in both lean and obese rats, whereas glucose led to rather enhanced insulin sensitivity. Leptin, body weight, and fat pad were not significantly altered by either fructose or glucose in the obese rats. These results suggest that dietary glucose stimulates leptin production by increasing adipose tissue or stimulating glucose metabolism in lean rats. Hyperleptinemia in VMH-lesioned rats is associated with both increased adiposity and hyperinsulinemia but not with insulin resistance. Dietary fructose does not alter leptin levels, although this sugar brings about hyperinsulinemia and insulin resistance, suggesting that hyperinsulinemia compensated for insulin resistance does not stimulate leptin production.

Aims/IntroductionTo explore the relationships between periodontitis and microvascular complications as well as glycemic control in type 2 diabetes patients.Materials and MethodsThis multicenter, hospital‐based, cross‐sectional study included 620 patients with type 2 diabetes. We compared the prevalence and severity of periodontitis between patients with ≥1 microvascular complication and those without microvascular complications. We also compared the prevalence and severity of periodontitis among patients with different degrees of glycemic control.ResultsAfter adjusting for confounding factors, multiple logistic regression analysis showed that the severity of periodontitis was significantly associated with the number of microvascular complications (odds ratio 1.3, 95% confidence interval 1.1–1.6), glycated hemoglobin ≥8.0% (64 mmol/mol; odds ratio 1.6; 95% confidence interval 1.1–2.3), and older age (≥50 years; odds ratio 1.7; 95% confidence interval 1.1–2.6). However, the prevalence of periodontitis was not significantly associated with the number of microvascular complications, but was associated with male sex, high glycated hemoglobin (≥8.0% [64 mmol/mol]), older age (≥40 years), longer duration of diabetes (≥15 years) and fewer teeth (≤25). Furthermore, propensity score matching for age, sex, diabetes duration and glycated hemoglobin showed that the incidence of severe periodontitis was significantly higher among patients with microvascular complications than among those without microvascular complications (P < 0.05).ConclusionsThe number of microvascular complications is a risk factor for more severe periodontitis in patients with type 2 diabetes, whereas poor glycemic control is a risk factor for increased prevalence and severity of periodontitis.

The mechanisms of marked increase in plasma leptin soon after ventromedial hypothalamus (VMH) lesions were investigated. Although rats did not gain body weight or parametrial fat-pad mass 24 h after the operation, the acute VMH-lesioned rats exhibited substantial five- and fourfold increases in plasma leptin levels compared with sham-operated control rats in fed (22.6 +/- 3.2 vs. 5.8 +/- 1.2 ng/ml) and fasted (8.8 +/- 2.0 vs. 2.3 +/- 0.3 ng/ml) states, respectively. Plasma insulin concentration was doubled in VMH-lesioned rats compared with sham-operated controls in both fed and fasting states. Northern blot analysis revealed that mRNA of ob gene was not increased in parametrial fat pad of animals 24 h after the creation of VMH lesions. However, leptin content in the fat pad was significantly increased in VMH-lesioned rats compared with sham-operated controls (32.2 +/- 4.7 vs. 17.4 +/- 2.3 ng/g wet tissue). The leptin content in parametrial fat pad was highly correlated with plasma leptin concentrations (r = 0.898, P < 0.001). To define the effect of hyperinsulinemia on their hyperleptinemia, a small dose of streptozotocin (STZ) (25 mg/kg body wt) was intravenously administered into rats 5 days before the creation of VMH lesions. Plasma insulin levels were not increased after VMH lesions in STZ-pretreated rats. Plasma leptin levels were halved in the absence of hyperinsulinemia, but still remained twofold higher than those in their sham-operated counterparts (9.9 +/- 1.3 vs. 4.8 +/- 0.7 ng/ml). These results indicate that the destruction of VMH rapidly promotes leptin production before obesity develops through an enhanced translational process in which hyperinsulinemia occurring after VMH lesioning plays an important role. The present study also suggests that there are other mechanisms that rapidly upregulate leptin production in adipocytes in VMH-lesioned rats in which the target organ of this hormone has been destroyed.

Recent work has shown that high-density lipoprotein (HDL) isolated from human atherosclerotic lesions and the blood of patients with established coronary artery disease contains elevated levels of 3-nitrotyrosine and 3-chlorotyrosine. A higher nitrotyrosine content in lipoprotein is significantly associated with diminished cholesterol efflux capacity of the lipoprotein. Since accelerated atherogenesis is a key complication of diabetes mellitus, and nitrosative stress has recently been implicated in diabetic pathology, we set out to demonstrate an increase in the circulating levels of nitrated apolipoprotein A (apoA)-I in type 2 diabetic patients and its putative correlation with metabolic biomarkers. In this work we addressed this hypothesis in a case-control study with 30 type 2 diabetic patients and 30 age-matched control subjects. Nitrated apoA-I was 3280+/-1910 absorbance peak area/apoA-I (g/L) for diabetic patients and 2320+/-890 for control subjects (p<0.037). This represents a 50% increase in circulating nitrated apoA-I in diabetic patients to age-matched controls. Diabetic patients also showed increases of a similar magnitude in circulating advanced glycation endproducts measured as pentosidine fluorescence (44.16+/-16.26 vs. 30.84+/-12.86 AU; p<0.01) and in circulating lipoperoxides (46.0+/-18.0 vs. 37.2+/-18.0 nmol/L; p<0.03). No significant correlation was found between nitration of apoA-I and glycosylated hemoglobin or any of the other parameters measured. If proven in subsequent functional and in vivo studies, increased nitrated apoA-I would represent another mechanism by which nitrosative stress participates in diabetic macro-angiopathy.

To explore the role of adiposity on hypertriglyceridemia associated with obesity, we examined the relation between triglyceride secretion rate (TGSR) and plasma leptin, insulin, or insulin resistance in ventromedial hypothalamus (VMH)-lesioned rats in the dynamic and static phases (2 and 14 wk after lesions, respectively). VMH-lesioned rats gained body weight (BW) at fivefold higher rates in the dynamic phase compared with sham-operated control (sham) rats, and BW gain reached a plateau in the static phase. Parametrial fat pad mass was increased 2.5-fold in VMH-lesioned rats compared with sham rats in both phases. Leptin levels were sixfold higher in VMH-lesioned rats of the dynamic phase and even higher in the static phase. Insulin levels were twofold higher in VMH-lesioned rats than in sham rats in both phases. In the dynamic phase, VMH-lesioned rats had 2-fold higher plasma triglyceride (TG) levels and 2.6-fold higher TGSRs, whereas steady-state plasma glucose (SSPG) values, an indicator of insulin resistance, were lower. SSPG values became significantly higher in VMH-lesioned rats in the static phase, but TGSR was not further accelerated. TGSR was significantly associated with leptin, independent of insulin. Leptin was highly correlated with BW, fat mass, and nonesterified fatty acids (NEFA). These results suggest that adiposity itself plays a critical role in TGSR probably through increased NEFA flux from enlarged adipose tissues. Insulin resistance is not associated with the overproduction of TG in this animal model for obesity.