Obesity Diabetes Mellitus Research Articles

Increased BMR in overweight and obese patients with type 2 diabetes may result from an increased fat-free mass.

The study aimed to determine the relationships between the basal metabolic rate (BMR) and body composition of overweight and obese Chinese adults with type 2 diabetes mellitus (DM). This cross-sectional clinical study enrolled 193 Chinese adults with type 2 DM who were overweight (24 kg/m(2)=BMI≤28 kg/m(2), n=99), or obese (BMI ≥28 kg/m(2), n=94). Ninety-seven adults with normal BMIs, including 50 DM patients and 47 healthy adults, were recruited as a control group. BMR was measured by indirect calorimetry; predicted BMR was calculated according to the Schofield equation; and the relationships between BMR, body composition, and biochemical results were determined by the Pearson correlation. The results showed that obese DM patients had significantly higher BMRs than both overweight patients (P<0.05) and patients with normal BMI did (P<0.05). The measured BMR was significantly lower than the predicted BMR (P<0.05) in all groups. Obese and overweight DM patients had significantly greater weight, waist circumference, hip circumference, BMI, body surface area, body fat percentage, fat mass, and fat-free mass than patients with normal BMI. Except for waist circumference, these body composition measurements were significantly increased in obese DM patients when compared with those in overweight DM patients (P<0.05). Fat-free mass was closely correlated with BMR in both DM patients (r=0.874, P<0.01) and in healthy controls (r=0.902, P<0.01). It was concluded that overweight and obese Chinese adults with type 2 DM had increased BMRs compared with normal-weight controls, which may result from the difference in fat-free mass.

Abstract 16008: Association Between Statin Exposure and Diabetes Incidence in a Nationwide Claims Database

Background: Statins reduce risk for cardiovascular events; however, concerns have been raised about their association with diabetes mellitus (DM). We used a national health insurance claims database, which captures the health care experiences of &gt;50 million privately insured individuals, to determine if there was a significant association between statin exposure and incidence of DM when controlling for multiple covariates not accounted for in prior analyses. Method: A cohort of non-diabetic patients who initiated treatment with a statin was matched with a control group of patients who did not receive a statin based on age, gender and geographic location. Patients were then followed for a minimum of 2 years to determine whether they developed DM (i.e. ≥2 ICD-9 code for DM and/or pharmacy claim for DM medications). In addition to Pearson chi-square tests for unadjusted comparisons, Cox proportional hazard models were used to examine the relationship between statin exposed and unexposed groups adjusting for HTN, CAD, PAD, CVA, CHF, hyperlipidemia and healthcare costs in the prior year. Predefined subgroup analyses were performed based on age, gender, obesity status and statin type. Results: The study population included 231,478 matched pairs of exposed and unexposed subjects (age 51.3 ±7.5 years; follow up duration of 1140 ±212.77 days). Statin exposure was associated with an increased DM incidence [adjusted HR 2.236 (2.182, 2.291)]. However, the effect was significant only after the age of ≥50 years [for age groups 30-39, 1.0 (0.86, 1.163); 40-49, 1.053 (0.91, 1.22); 50-59, 1.19 (1.028, 1.374); 60-69, 1.276 (1.101, 1.478) with age group 20-29 as reference]. Compared to males, statin-exposed females had an increased incidence of DM [HR 1.08 (1.06, 1.10)]. In obese individuals DM incidence was 1.820 (1.610, 2.057) in statin exposed versus unexposed. All statin types were associated with increased DM incidence without any statistically significant differences between them. Conclusion: In this large study, there was an association between statin exposure and diabetes incidence. These findings are consistent with other data reported in literature and strengthen the causal link between statin exposure and diabetes.

Activating brown adipose tissue for weight loss and lowering of blood glucose levels: a microPET study using obese and diabetic model mice.

PurposeThis study aims at using 18F-FDG microPET to monitor the brown adipose tissue (BAT) glucose metabolism in obese and diabetic mouse models under different interventions, and study the therapeutic potential of BAT activation for weight loss and lowering of blood glucose in these models.MethodsObese mice were established by a high-fat diet for eight weeks, and diabetes mellitus(DM) models were induced with Streptozocin in obese mice. 18F-FDG microPET was used to monitor BAT function during obese and DM modeling, and also after BRL37344 (a β3-adrenergic receptor agonist) or levothyroxine treatment. The BAT function was correlated with the body weight and blood glucose levels.ResultsCompared with the controls, the obese mice and DM mice showed successively lower 18F-FDG uptake in the interscapular BAT (P = 0.036 and <0.001, respectively). After two-week BRL37344 treatment, the BAT uptake was significantly elevated in both obese mice (P = 0.010) and DM mice (P = 0.004), accompanied with significantly decreased blood glucose levels (P = 0.023 and 0.036, respectively). The BAT uptake was negatively correlated with the blood glucose levels in both obese mice (r = −0.71, P = 0.003) and DM mice (r = −0.74, P = 0.010). BRL37344 treatment also caused significant weight loss in the obese mice (P = 0.001). Levothyroxine treatment increased the BAT uptake in the control mice (P = 0.025) and obese mice (P = 0.013), but not in the DM mice (P = 0.45).ConclusionThe inhibited BAT function in obese and DM mice can be re-activated by β3-adrenergic receptor agonist or thyroid hormone, and effective BAT activation may lead to weight loss and blood glucose lowering. Activating BAT can provide a new treatment strategy for obesity and DM.

Hypoxemia and glycemic control in type 2 diabetes mellitus with extreme obesity.

Obstructive sleep apnea (OSA) has been shown to be associated with type 2 diabetes mellitus (DM). Studies on healthy individuals found that OSA is associated with lower insulin sensitivity. We hypothesized that nocturnal hypoxemia from OSA is associated with poorer glycemia in severely obese DM individuals. This was a retrospective observational study of 122 non-DM, 126 non-insulin-treated DM, and 35 insulin-treated DM patients. Data were collected on demographic characteristics, body mass index, and comorbidities. An overnight sleep study was performed in all patients, and OSA was defined as an apnea-hypopnea index of ≥5 events/h. There were more males (P = .003) and a lower proportion of white Europeans (P = .010) among DM patients. The prevalence of OSA was 80.1% in DM and 63.1% in non-DM individuals (P = .001). DM individuals also had lower oxygen saturation (O2) (P = .0106), greater percentage of time spent under 90% oxygen saturation (%TST<90%) (P = .0067), and higher apnea-hypopnea index (P = .0085). Regression analysis showed that %TST<90% and minimum O2 saturations were associated with worse hemoglobin A1c results among DM individuals. Every 10% reduction in minimum O2 was associated with a 0.3% increase in HbA1c, whereas a 10% increase in %TST<90% was associated with a 0.2% increase in hemoglobin A1c after adjusting for a range of potential confounders. The high OSA prevalence in DM individuals and a positive relationship between nocturnal hypoxemia and glycemia supports the need to assess correction of hypoxemia as a management strategy for glycemic control.

Diabetes mellitus leads to accumulation of dendritic cells and nerve fiber damage of the subbasal nerve plexus in the cornea.

To evaluate whether nerve fibers of the subbasal nerve plexus (SNP) and dendritic cells (DCs) are in association with each other leading to neuropathy in the diabetic cornea. BALB/c mice were injected with streptozotocin (STZ) for 5 days for induction of diabetes mellitus (DM) or with vehicle solution (control). B6.VLep(ob/ob) (ob/ob) mice served as an obese and glucose-intolerant DM type 2 (DM II) model and lean B6.VLep(ob/+) (ob/+) mice as respective controls. Using in vivo corneal confocal microscopy (CCM), nerve fibers and DCs were quantified over a period of 9 weeks and additionally analyzed by in vitro immunofluorescence whole-mount staining. In STZ-diabetic mice, CCM revealed an increase of DC density (DCD) in contrast to controls, whereas nerve fiber density (NFD) was decreased with duration of DM. In ob/ob mice, DCD was 3-fold higher than in both ob/+ mice and STZ-diabetic mice. Whole-mount staining displayed CD11c(+) and major histocompatibility complex (MHC) class II(+) mature DCs in colocalization with class III β-tubulin(+) nerve fibers in the cornea. Hyperglycemia leads to corneal DC infiltration, and obesity aggravates this immune response. The direct contact between DCs and the SNP can be assumed to be a trigger of nerve fiber damage and thus a contributing factor to polyneuropathy in diabetic corneas.

Functional and structural alterations in urinary bladder of an obese Zucker rat model

Diabetic bladder dysfunction (DBD) is a most common complication of diabetes mellitus (DM), and is seen in 40–80% of diabetic patients. It is characterized by impaired bladder sensation, increased bladder capacity, decreased bladder contractility and increased residual urine. The goals of these studies were to test the hypothesis that the obese Zucker rat is an appropriate model for type 2 diabetic bladder investigations and to define the alterations in bladder structure and functional responses in this setting. Histological examination of bladder cross sections was shown that total bladder wall thickness and threshold pressure of voiding were significantly increased in obese rats, while voiding time, maximal intravesical pressure and intercontraction intervals significantly declined as compared to age‐matched lean rats, respectively. Contractile responses of obese DM strips to Aceltylchine (Ach) and KCl were significantly less than those of bladder strips from lean animals. In addition to generating less force, it can also be seen that strips from the obese DM strips showed slower rate of force development than strips from lean animals. Two major myosin isofroms, SM1 and SM2 myosin heavy chains (MHCs) were separated, estimated and the ratios averaged shown that the SM2‐to‐SM1 isoform ratios were declined in obese bladders. After 12 % SDS‐PAGE, transfered and immunoreacted with antibody against tropomyosin (Tm) and α‐actin (as an internal control), the Tm/α‐actin ratios increased in obese bladders as compared to age‐matched lean bladders. All the data indicated that the obese Zucker rat is a relevant model for type 2 diabetic bladder investigations than the streptozotocin‐induced animal model.

Interrelationship between coagulation factor VII and obesity in diabetes mellitus (type 2)

We explored the interrelationships of coagulation FVII activity levels with obesity, leptin and insulin resistance in diabetes mellitus (DM Type 2) and in non-diabetic control subjects. We found FVII hypercoagulant activity levels in DM not associated with obesity, leptin levels or insulin resistance. It was found independently associated with hypertriglyceridemia.

Obesity as risk factor and study of obesity related proteins in diabetes mellitus

Obesity is one of the leading cause of diabetes mellitus in the world population due to the growing trend of sedentary lifestyle and increased food consumption of high caloric diet. A concomitant increase due to this has been observed in coronary heart diseases, hypertension and even diabetes. High lipid profile of the serum is one of the factors that may result in the development of obesity in diabetes mellitus and thus the progression of diabetes. This study was carried out to determine the effect of various physical and biochemical parameters of obesity to ascertain the link to presence and severity of diabetes. For this purpose physical parameters such as BMI, waist circumference, and biochemical parameters such as FBS, glycated HbA1c, albumin excretion rate, urine creatinine level, and lipid profile parameters such as cholesterol, triglyceride, HDL, LDL and VLDL were measured by standard referred protocols. Elevated serum leptin level was associated with components of the metabolic syndrome, including increased body-mass index, waist-to-hip ratio, serum triglyceride levels, fasting blood sugar, glyacated HbA1c, total serum proteins and decreased high-density lipoprotein cholesterol levels in obese diabetes as compared to lean, non-obese and normal subjects. The results were found to be significant with p biochemical parameters are greater in obese diabetes as compared to non-obese diabetes group and also in lean. Proteins levels such as leptin are also greater in obese diabetes as compared to non-obese and lean objects.

Insulin Resistance Is Associated with Increased Circulating Level of Thrombin-Activatable Fibrinolysis Inhibitor in Type 2 Diabetic Patients

Hypofibrinolysis is a common finding in patients with diabetes mellitus (DM) and obesity and a risk factor for the development of cardiovascular disease. Recently, a new potent inhibitor of fibrinolysis, the thrombin-activatable fibrinolysis inhibitor (TAFI) has been isolated and characterized from human plasma. The present study was undertaken to assess the activity and circulating level of TAFI and its relation to fibrinolytic function and obesity in patients with type 2 DM. Fifty-seven patients with type 2 DM (38 men, 19 women) were enrolled in this study. DM patients were categorized in age-matched obese [body mass index (BMI) > or = 25] and nonobese (BMI < 25) groups. The plasma concentration and activity of TAFI were significantly (P < 0.05) higher in DM patients than in healthy controls. The plasma levels and activity of TAFI were significantly (P < 0.05) elevated in obese DM patients compared with nonobese DM and nonobese healthy subjects. RT-PCR demonstrated the expression of TAFI in human adipose tissue and in human endothelial cells. The plasma levels of TAFI were independently and significantly correlated with glucose intolerance (HbA(1c)), with obesity (BMI, visceral fat area), and with an indicator of insulin resistance (glucose infusion rate). This study showed that increased circulating level of TAFI may be an important causative factor of hypofibrinolysis in patients with type 2 diabetes, obesity and insulin resistance.

Thigh adipose tissue distribution is associated with insulin resistance in obesity and in type 2 diabetes mellitus

Adipose tissue (AT) content of the thigh is generally not considered to be associated with insulin resistance (IR), but it is unclear whether the distribution of AT in the thigh is a determinant of IR. We investigated whether subcompartments of AT within the thigh are determinants of IR. Midthigh AT, muscle composition, and insulin sensitivity were compared in 11 obese patients with type 2 diabetes mellitus (DM); 40 obese, glucose-tolerant (GT) and 15 lean, GT volunteers; and 38 obese subjects who completed a weight-loss program. Midthigh AT area measured with computed tomography was partitioned into 3 components: subcutaneous AT (SCAT), AT beneath the fascia (SFAT), and AT infiltrating muscle groups (IMAT). Muscle attenuation characteristics were determined. Obese DM and obese GT subjects had lower insulin sensitivity than lean GT subjects. SCAT was greater in obesity, yet did not correlate with insulin sensitivity. SFAT was approximately 8% of total thigh AT and correlated with insulin sensitivity. IMAT was highest in obese DM, and although it accounted for only approximately 3% of thigh AT, it was a strong correlate of insulin sensitivity. Mean attenuation was highest in lean subjects and was associated with higher insulin sensitivity. Weight loss reduced the amount of thigh AT, the proportion of thigh IMAT, and the amount of low-density thigh muscle. SFAT and IMAT are markers of IR in obesity and DM although they are much smaller than SCAT, which does not predict IR. Muscle composition reflecting increased fat content is also associated with IR.

The role of obesity in diabetes mellitus

The role of obesity in diabetes mellitus

Management of obesity in diabetes mellitus.

A primary goal of treatment in obese individuals with NIDDM is weight loss and maintenance. Obesity is a precipitating factor for the development of NIDDM in individuals who are genetically at risk. A variety of weight-loss regimens are available to match the specific needs and lifestyles of individuals. Hypocaloric high-fiber diets have been found to be effective in achieving weight loss, as well as aiding in glycemic and lipid control. Very low calorie diets, administered under medical supervision, are useful for obese NIDDM patients with 18-55 kilograms of weight to lose. Lifestyle education appears to be an important element of any successful weight loss program.