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In adults, visceral fat accumulation is associated with insulin resistance and dyslipidemia. The cause-and-effect nature of these relationships is not clear. The objective of the present study was to determine if similar relationships exist in prepubertal children. Specifically, we determined whether visceral fat was associated with fasting insulin, insulin sensitivity (Si), serum triglyceride (TG) concentration, or serum HDL cholesterol (HDL-C) concentration; whether visceral fat or Si was independently related to lipids; and whether ethnicity influenced the relationship between visceral fat and risk factors. Subjects were 61 prepubertal African-American and Caucasian children. Total body fat was determined by dual-energy X-ray absorptiometry, visceral fat by computed tomography, and insulin sensitivity by the tolbutamide-modified, frequently sampled intravenous glucose tolerance test with minimal modeling. In multiple linear regression analysis (adjusting for total fat, sex, and ethnicity), visceral fat was independently related to TG (P < 0.05) and fasting insulin (P < 0.001), but not Si (P = 0.425). Total body fat was independently related to Si (P < 0.001). Si was independently related to fasting insulin (P < 0.001) but not to TG or HDL-C (P = 0.941 and 0.201, respectively). Si in African-Americans was 42% lower than in Caucasians (0.50 +/- 0.05 vs. 0.86 +/- 0.11 x 10(-5) min(-1) x pmol(-1) x l, mean +/- SE after adjusting for total fat, P < 0.001). Nonetheless, ethnicity was not independently related to either TG or HDL-C (P = 0.075 and 0.619, respectively, after adjusting for total and visceral fat and sex). The slopes of the relationships of total and visceral fat with risk factors did not differ with ethnicity. In conclusion, visceral fat appears metabolically unique in children, being independently associated with elevated TG and insulin but not Si. Obese children and African-American children were more insulin resistant, independent of visceral fat accumulation. Lower Si was associated with higher, faster insulin, but not dyslipidemia. Thus, obesity, visceral fat accumulation, and ethnicity in children may confer negative, but independent, health risks.
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PMID:Visceral fat, insulin sensitivity, and lipids in prepubertal children. 1042 67

Type 2 diabetes mellitus is a chronic disease which causes neurologic, cardiac, vascular, ocular and renal complications. The present study documented the prevalence of diabetes and associated risk factors in 1774 adults who were older than 30 years. An oral glucose tolerance test (OGTT) was conducted according to the World Health Organization (WHO) criteria. Of the 1452 subjects, 58 (4%) had diagnosed diabetes, 41 (2.9%) undiagnosed diabetes and 130 (9%) had impaired glucose tolerance. The total glucose intolerance was 15. 9%. The prevalences of type 2 diabetes mellitus (9.7%-4.1%) were significantly different in low occupational and high occupational activity groups, respectively (P<0.0001). The prevalence of type 2 diabetes mellitus was 17.9% among the hypertensive group (P<0.0001). The prevalence of type 2 diabetes mellitus was higher in smokers (P<0.05). Patients with diagnosed diabetes, undiagnosed diabetes and IGT were older, more obese and have higher blood glucose values, triglyceride values, systolic and diastolic blood pressures than healthy subjects (P<0.001). We conclude that type 2 diabetes mellitus and IGT prevalences are quite high in the urban area of Kayseri, central Anatolia and multivariate analysis indicated that low occupational activity, low leisure activity, family history for diabetes, hypertension and obesity were significant independent risk factors for diabetes mellitus.
Acta Diabetol 1999 Jun
PMID:The prevalence and identification of risk factors for type 2 diabetes mellitus and impaired glucose tolerance in Kayseri, central Anatolia, Turkey. 1043 58

Type 2 (non-insulin-dependent) diabetes is emerging as a leading chronic non-communicable disease among the adult Kuwaiti population. Based on the World Health Organization and similar reports the projected estimates for subjects suffering from type 2 diabetes by the years 2000 and 2010 show a striking tendency to high rates of the disease in our area. We report the prevalence rates of glucose intolerance among a relatively young adult Kuwaiti population below 50 years of age and the effect of implementing the recent 1997 American Diabetes Association diagnostic criteria on the frequency of type 2 diabetes, impaired glucose tolerance and impaired fasting glucose among this group. The overall prevalence rate for the three categories of glucose intolerance reached as high as 15.8% (95% CI, 14.2 to 17.4). Age, though all subjects were below 50 years, parental history of type 2 diabetes, diastolic blood pressure and serum triglycerides were found to be significant associated risk factors for the development of type 2 diabetes. Obesity was an apparent significant factor associated with the three forms of glucose intolerance (p < 0.001). Obesity and physical inactivity were documented in both non-diabetic and more so in diabetic Kuwaiti adults, which should form the basis of any immediate intervention programme. An integrated approach to the prevention of the described critical risk factors associated with type 2 diabetes is highly recommended in Kuwait. Research, focused on genetics of type 2 diabetes in the highly susceptible Kuwaiti population, should be planned.
Acta Diabetol 1999 Sep
PMID:Impact of the 1997 American Diabetes Association criteria on classification of glucose intolerance among Kuwaitis below 50 years of age. 1066 17

There are contrasting data about the relationship between obesity and macrovascular complications in type 2 diabetes mellitus, and it is not known if risk factors for coronary artery disease are different in normal weight and overweight or obese patients. All 2113 patients with type 2 diabetes mellitus referring to the Diabetic Clinic of Asti were studied. Patients were divided into tertiles of body mass index, according to their sex (BMI < 26.9; >/= 26.9 and < 31.4; >/= 31.4 kg/m(2) for females and BMI < 25.7; >/= 25.7 and < 28.8; >/= 28.8 kg/m(2) for males). Age, BMI, duration of diabetes, blood pressure, HbA(1c) total cholesterol, HDL-cholesterol, LDL-cholesterol, and prevalence of insulin treatment and hypertension were higher in females, whereas exercise, alcohol intake, smoking habits and prevalence of dyslipidemia were higher in males. An increase in BMI was associated with an increase in HbA(1c), number of cigarettes/day, blood pressure, triglycerides, C-peptide, prevalence of hypertension and dyslipidemia, and with a decrease in age, duration of diabetes and HDL-cholesterol values. In spite of an apparently worse cardiovascular risk profile, females showed a 50% lower prevalence of CAD than males and the prevalence of CAD was not significantly different in obese compared to other BMI categories. Multiple logistic regression showed that risk factors for CAD were different in males and females and similar in the lower tertiles of BMI, while different in the highest. In obese females, risk factors for CAD were age, reduced HDL-cholesterol and increased HbA(1c) levels; in males they were years of smoking and duration of diabetes. These data suggest that in type 2 diabetes, risk factors for CAD are different in the two sexes and in patients with the highest BMI compared to the normal and overweight subjects; blood glucose control and duration of diabetes seem more important than conventional cardiovascular risk factors in obese patients.
Acta Diabetol 1999 Sep
PMID:Sex- and BMI-related differences in risk factors for coronary artery disease in patients with type 2 diabetes mellitus. 1066 19

Recently, two G-->A polymorphisms at positions -308 and -238, in the promoter of the tumor necrosis factor alpha (TNF-alpha) gene, have been identified. These variants have, in different ethnic groups, been linked to estimates of insulin resistance and obesity. The objective of the present study was to investigate whether these genetic variants of TNF-alpha were associated with features of the insulin resistance syndrome or alterations in birth weight in two Danish study populations comprising 380 unrelated young healthy subjects and 249 glucose-tolerant relatives of type 2 diabetic patients, respectively. All study participants underwent an iv glucose tolerance test with the addition of tolbutamide after 20 min. In addition, a number of biochemical and anthropometric measures were performed on each subject. The subjects were genotyped for the polymorphisms by applying PCR restriction fragment length polymorphism. Neither of the variants was related to altered insulin sensitivity index or other features of the insulin resistance syndrome (body mass index, waist to hip ratio, fat mass, fasting serum lipids or fasting serum insulin or C-peptide). Birth weight and the ponderal index were also not associated with the polymorphisms. In conclusion, although the study was carried out on sufficiently large study samples, the study does not support a major role of the -308 or -238 substitutions of the TNF-alpha gene in the pathogenesis of insulin resistance or altered birth weight among Danish Caucasian subjects.
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PMID:The -238 and -308 G-->A polymorphisms of the tumor necrosis factor alpha gene promoter are not associated with features of the insulin resistance syndrome or altered birth weight in Danish Caucasians. 1077 Feb 22

This study examined whether the simultaneous presence of the previously identified Trp/Arg64 polymorphism of the beta3-adrenergic receptor (BAR) gene and the -3826 A-->G nucleotide variant of the uncoupling protein-1 (UCP1) gene are associated with obesity, insulin resistance, or alterations in size at birth in a Danish study population comprising 379 unrelated young Caucasian subjects. All study participants underwent an iv glucose tolerance test with addition of tolbutamide after 20 min. In addition, a number of biochemical and anthropometric measures were performed on each subject. The subjects were genotyped for the 2 polymorphisms by applying PCR-restriction fragment length polymorphism. The subjects were divided into 4 groups according to their BAR and UCP1 genotype: wild-type carriers (n = 184), only Trp/Arg64 carriers (n = 29), only A-->G UCP1 carriers (n = 146), and carriers of both genetic variants (n = 20). There were no differences across the genotype groups with respect to body mass index, fat mass, waist to hip ratio, birth weight or length, ponderal index, or weight gain during childhood or adolescence, nor was the combined genotype related to alterations in fasting serum levels of lipids, insulin, or C peptide or the insulin sensitivity index. In conclusion, the present study failed to demonstrate an additive or synergistic effect of the Trp/Arg64 variant of the BAR gene and the -3826 A-->G variant of the UCP1 gene on the development of obesity and insulin resistance among randomly recruited Danish Caucasian subjects.
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PMID:Studies of the synergistic effect of the Trp/Arg64 polymorphism of the beta3-adrenergic receptor gene and the -3826 A-->G variant of the uncoupling protein-1 gene on features of obesity and insulin resistance in a population-based sample of 379 young Danish subjects. 1099 1

The arcuate nucleus (AN) of the hypothalamus is a key area in which endocrine messages are relayed to the brain, while midbrain raphe nucleus (RN) is the source of brain serotonin. Both nuclei contribute to the central mechanism of energy homeostasis. This experiment aimed to determine the impact of AN and RN grafts on insulinemia and obesity in diabetic rats. AN and RN were dissected from 15-day (Fa/Fa) lean embryos and grafted separately or together into the third brain ventricle of obese (fa/fa) male Zucker rats. Histological analysis showed the functional maturity of grafts, which were vascularized, contained neurons reinnervating the periventricular hypothalamus and hypophysis, and expressed neuropeptide Y and enzymes for dopamine and serotonin synthesis. Three months after transplantation, the rats grafted with AN or RN had a lower body weight gain compared to sham-operated rats (19% and 17%, respectively). Rats grafted with AN together with RN gained significantly less body weight than rats grafted with AN or RN separately (31% vs. sham-operated rats), and showed a decreased plasma insulin concentration (132 +/- 33 microU/ml) vs. sham-operated rats (459 +/- 108 microU/ml, p < 0.05). A synergistic effect on alleviating obesity and insulinemia by double AN and RN grafts suggests that both these nuclei are functionally interrelated in maintaining energy homeostasis, and normal functioning of both nuclei is altered during obesity.
Acta Diabetol 2000
PMID:Synergistic effect of arcuate and raphe nuclei graft to alleviate insulinemia and obesity in Zucker rats. 1119 29

Neuromedin B has been shown to exert an inhibiting effect on food consumption in rats. The corresponding gene NMB maps to chromosome 15q22.3-q23, a region expected to contain a gene for the Bardet-Biedl syndrome type 4 (BBS4). Based on its map position and the putative function of the encoded peptide, NMB can be considered as a candidate gene both for BBS4 and the development of human obesity. To examine its involvement in these phenotypes, we determined the genomic structure of human NMB, and performed a mutation screen in its coding region. In genomic DNA of six BBS4 patients and in a large population sample, two sequence variants were detected: a g.253C-->A transversion creating a P73T substitution and a g.401G-->A silent mutation changing the stop codon TGA into stop codon TAA. A case-control study with 92 extremely obese patients and 94 underweight students revealed a significant association between the g.401G-->A polymorphism and body weight (adjustedp = 0.03), which was confirmed in a validation sample consisting of 95 extremely obese patients, and 95 normal weight and 48 underweight individuals (Mann-Whitney p = 0.02). These results suggest a contribution of NMB or a gene in its close vicinity to genetic weight control in humans.
Acta Diabetol 2000
PMID:Significant association between a silent polymorphism in the neuromedin B gene and body weight in German children and adolescents. 1119 34

Obesity is associated with hyperinsulinemia and reduced insulin sensitivity, both risk factors for type 2 diabetes. However, it is not clear whether these risk factors occur as a result of obesity or whether they contribute to the development of obesity. The aims of this study were to determine whether baseline (first visit) or changes in insulin measures over time were associated with longitudinal changes in body fat mass during growth in children. The study group consisted of 137 children (83 Caucasian and 54 African American) with a mean age of 8.1 yr at baseline. The children returned for 3-6 annual visits for measurement of fasting insulin, insulin sensitivity (Si), and acute insulin response (AIR) from the tolbutamide-modified frequent sampling iv glucose tolerance test and for determination of body composition by dual energy x-ray absorptiometry. Data were analyzed using SAS Proc mixed growth models. Total fat mass increased with time by 15.6%/yr (P = 0.013), but the rate of increase was not significantly influenced by race, sex, or Tanner stage. However, fasting insulin (positive effect), Si (negative effect), and AIR (positive effect) were significantly associated with the rate of increase in fat mass. In conclusion, in this cohort of children, growth-related increases in body fat were significantly associated with increases in fasting insulin and AIR and decreases in Si.
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PMID:Longitudinal changes in body fat in African American and Caucasian children: influence of fasting insulin and insulin sensitivity. 1144 86

Energy homeostasis is the balance between energy intake and energy expenditure. Assessment of energy intake is unreliable, especially in obese individuals. On the contrary it is possible to assess energy expenditure by means of different techniques. In this review, the contributions of indirect calorimetry to its assessment and to the comprehension of the pathogenic mechanisms of obesity and diabetes mellitus are discussed. Knowledge regarding energy expenditure and its components (basal metabolic rate, food-induced thermogenesis, expenditure related to physical activity), obtained in obese individuals by means of indirect calorimetry, is summarized. The effects of dietetic manipulation of the relative fractions of macronutrients (fat, carbohydrate and protein) and fiber intake on energy expenditure are described with implications regarding the pathogenesis of obesity. Besides environmental factors, energy expenditure is strongly influenced by inherited features. The application of indirect calorimetry to study recently discovered polymorphisms of genes strongly related to energy expenditure in humans is also summarized. The role of indirect calorimetry in the identification of the glucose metabolic pathways (oxidative and non-oxidative) affected in the insulin resistance syndrome is also described. Indirect calorimetry has been useful in realizing that the alterations typical of insulin resistance are reproducible in vivo in healthy humans, increasing the availability of free fatty acids. In fact, indirect calorimetry contributed to understanding the in vivo mechanisms of substrate competition, which was hypothesized more than forty years ago. In this field of application, the identification of simple (non-invasive and inexpensive) markers of insulin resistance is urgent for primary and secondary prevention of these diseases with high morbidity and mortality. The postabsorptive assessment of resting energy expenditure and macronutrient partitioning in fuel metabolism may be helpful and is discussed with advantages and limitations. The treatment of multifactorial diseases will probably require the use of poly-therapeutic interventions. In fact, drugs that act purely on one pathogenic factor of these diseases frequently fail. To better design strategic therapeutic approaches for each patient, to achieve significant long-term efficacy in the treatment of these diseases and to prevent their complications, indirect calorimetry has to be considered a landmark of quality control for nutritional support.
Acta Diabetol 2001
PMID:Pathogenesis of obesity and diabetes mellitus: insights provided by indirect calorimetry in humans. 1148 78


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