Nicola Abate

Relationships of generalized and regional adiposity to insulin sensitivity in men.

The relative impacts of regional and generalized adiposity on insulin sensitivity have not been fully defined. Therefore, we investigated the relationship of insulin sensitivity (measured using hyperinsulinemic, euglycemic clamp technique with [3-3H]glucose turnover) to total body adiposity (determined by hydrodensitometry) and regional adiposity. The latter was assessed by determining subcutaneous abdominal, intraperitoneal, and retroperitoneal fat masses (using magnetic resonance imaging) and the sum of truncal and peripheral skinfold thicknesses. 39 healthy middle-aged men with a wide range of adiposity were studied. Overall, the intraperitoneal and retroperitoneal fat constituted only 11 and 7% of the total body fat. Glucose disposal rate (Rd) and residual hepatic glucose output (rHGO) values during the 40 mU/m2.min insulin infusion correlated significantly with total body fat (r = -0.61 and 0.50, respectively), subcutaneous abdominal fat (r = -0.62 and 0.50, respectively), sum of truncal skinfold thickness (r = -0.72 and 0.57, respectively), and intraperitoneal fat (r = -0.51 and 0.44, respectively) but not to retroperitoneal fat. After adjusting for total body fat, the Rd and rHGO values showed the highest correlation with the sum of truncal skinfold thickness (partial r = -0.40 and 0.33, respectively). We conclude that subcutaneous truncal fat plays a major role in obesity-related insulin resistance in men, whereas intraperitoneal fat and retroperitoneal fat have a lesser role.

Relationship of Generalized and Regional Adiposity to Insulin Sensitivity in Men With NIDDM

Abdominal obesity, particularly excess intraperitoneal fat, is considered to play a major role in causing insulin resistance and NIDDM. To determine if NIDDM patients accumulate excess intraperitoneal fat, and whether this contributes significantly to their insulin resistance, 31 men with mild NIDDM with a wide range of adiposity were compared with 39 nondiabetic, control subjects for insulin sensitivity (measured using euglycemic-hyperinsulinemic clamp technique with [3-3H]glucose turnover) and total and regional adiposity (assessed by hydrodensitometry and by measuring subcutaneous abdominal, intraperitoneal, and retroperitoneal fat masses using magnetic resonance imaging [MRI], and truncal and peripheral skinfold thicknesses using calipers). MRI analysis revealed that intraperitoneal fat was not increased in NIDDM patients compared with control subjects; in both groups it averaged 11% of total body fat. NIDDM patients, however, had increased truncal-to-peripheral skinfolds thickness ratios. In NIDDM patients, as in control subjects, amounts of truncal subcutaneous fat showed a stronger correlation with glucose disposal rate than intraperitoneal or retroperitoneal fat; however, NIDDM patients were more insulin resistant at every level of total or regional adiposity. Further, no particular influence of excess intraperitoneal fat on hepatic insulin sensitivity was noted. We conclude that NIDDM patients do not have excess intraperitoneal fat, but that their fat distribution favors more truncal and less peripheral subcutaneous fat. Moreover, for each level of total and regional adiposity, NIDDM patients have a heightened state of insulin resistance.

The impact of ethnicity on type 2 diabetes

The rapid increase of diabetes prevalence in the US population and across all westernized world has been associated with environmental changes that promote obesity. Although dietary factors, such as total caloric intake, relative excess of dietary saturated fats content and lack of fibers, together with reduced level of physical activity clearly determine the main features of the obesogenic environment typical of western societies, the impact of lifestyle factors on obesity and diabetes appears to differ in various ethnic groups. Although ethnic-related differences in lifestyle factors may account for some of the predisposition to obesity and diabetes of various ethnic groups, genetic factors may play a more determinant role. These observations pose important public health questions in regard to strategies for treatment and prevention of diabetes both within the multiethnic US population and in the population of origin of various ethnicities. The elucidation of the pathophysiologic mechanisms responsible for the heterogeneous relationship between obesity and type 2 diabetes in various ethnicities may give important contributions to better understand the complex mechanisms involved in the development of this disease. This review examines epidemiological and pathophysiological aspects of the interaction between environment and ethnic predisposition to type 2 diabetes.

Insulin Resistance and Body Fat Distribution in South Asian Men Compared to Caucasian Men

Objective South Asians are susceptible to insulin resistance even without obesity. We examined the characteristics of body fat content, distribution and function in South Asian men and their relationships to insulin resistance compared to Caucasians. Research Design and Methods Twenty-nine South Asian and 18 Caucasian non-diabetic men (age 27±3 and 27±3 years, respectively) underwent euglycemic-hyperinsulinemic clamp for insulin sensitivity, underwater weighing for total body fat, MRI of entire abdomen for intraperitoneal (IP) and subcutaneous abdominal (SA) fat and biopsy of SA fat for adipocyte size. Results Compared to Caucasians, in spite of similar BMI, South Asians had higher total body fat (22±6 and 15±4% of body weight; p-value<0.0001), higher SA fat (3.5±1.9 and 2.2±1.3 kg, respectively; p-valueu200a=u200a0.004), but no differences in IP fat (1.0±0.5 and 1.0±0.7 kg, respectively; p-valueu200a=u200a0.4). SA adipocyte cell size was significantly higher in South Asians (3491±1393 and 1648±864 µm2; p-valueu200a=u200a0.0001) and was inversely correlated with both glucose disposal rate (r-valueu200a=u200a−0.57; p-valueu200a=u200a0.0008) and plasma adiponectin concentrations (r-valueu200a=u200a−0.71; p-value<0.0001). Adipocyte size differences persisted even when SA was matched between South Asians and Caucasians. Conclusions Insulin resistance in young South Asian men can be observed even without increase in IP fat mass and is related to large SA adipocytes size. Hence ethnic excess in insulin resistance in South Asians appears to be related more to excess truncal fat and dysfunctional adipose tissue than to excess visceral fat.

Ethnicity and type 2 diabetes: Focus on Asian Indians

Though the overall prevalence of type 2 diabetes is increasing in US and in all other westernized countries, significant differences are noted among different ethnic groups. The reasons for ethnic differences in the risk of type 2 diabetes are not entirely understood. For example, Asian Indians (people from India, Pakistan, and Bangladesh) have remarkably high prevalence of type 2 diabetes compared to Caucasians. However, the incidence of obesity, an important risk factor in the development of type 2 diabetes, is significantly lower in Asian Indians compared to Caucasians. Though westernization of lifestyle with dietary changes and lack of exercise may play a role in increased prevalence of type 2 diabetes in migrant Asian Indians, various epidemiological studies have shown that these factors alone are not sufficient to explain this trend. One important factor contributing to increased type 2 diabetes in Asian Indians is excessive insulin resistance compared to Caucasians. This difference in the degree of insulin resistance may be explained by either an environmental or a genetic factor or by combination of both. The understanding of the etiology and mechanisms causing increased insulin resistance in Asian Indians will provide clues to more effective prevention and treatment of diabetes in this ethnic group. Furthermore, the information may help in understanding the pathophysiology of type 2 diabetes in other ethnic groups and improve methods of treatment and prevention in all ethnic groups. Since the ethnic mix of the US population is changing rapidly and it is estimated that by the year 2020, over 50% of US population will include non-Caucasian ethnicity, the identification of the mechanism involved in the excessive development of type 2 diabetes in non-Caucasians becomes important. In this review, possible etiology of excessive insulin resistance and role of free fatty acids (FFA) in insulin resistance in Asian Indians is discussed. Finally, the role of targeting insulin resistance in prevention and treatment of diabetes is discussed.

Obesity and cardiovascular disease: Pathogenetic role of the metabolic syndrome and therapeutic implications

Since obesity is a major risk factor for cardiovascular disease (CVD), the increasing prevalence and degree of obesity in all developed countries has the potential to significantly offset the current efforts to decrease CVD burden in our population. Obesity is pathogenetically related to several clinical and sub-clinical abnormalities that contribute to the development of atherosclerotic placks and their complication, leading to the onset of cardiovascular events. Obesity seems to interact with inheritable factors in determining the onset of insulin resistance, a metabolic abnormality that is responsible for altered glucose metabolism and predisposition to type 2 diabetes, but that also has a major role in the development of dyslipidemia, hypertension and many other sub-clinical abnormalities that contribute to the atherosclerotic process and onset of cardiovascular events. Inheritable factors seem to modulate the onset of type 2 diabetes, dyslipidemia, hypertension and various insulin resistance-related sub-clinical abnormalities, often in a clustering pattern that is commonly referred to as the metabolic syndrome. Inheritable factors also are involved in the onset of CVD in a given population or individuals with various components of the metabolic syndrome. Intense research is currently undergoing to better understand the molecular mechanisms that could explain the relationship between environmental and inheritable factors that lead from obesity to atherosclerosis and cardiovascular event. The elucidation of these mechanisms will provide improved therapeutic strategies to reduce cardiovascular risk in the obese patients. However, effective therapeutic tools that control each of the known pathophysiological steps mediating CVD in obese patients are already available and should be used more aggressively. Patient education and coordinated approach of physicians, nurses and other health care providers in a multidisciplinary treatment of the obese patient is of fundamental importance to reduce CVD burden in our population.

Diet composition and the metabolic syndrome: what is the optimal fat intake?

Two cholesterol-raising fatty acids in the diet, saturated fatty acids and trans fatty acids, increase the serum low-density lipoprotein cholesterol concentration. This fact justifies the recommendation of a reduced intake of cholesterol-raising fatty acids. Emerging data suggest that diets higher in unsaturated fatty acids, particularly monounsaturated fatty acids, have several advantages over high-carbohydrate intakes. This advantage appears to hold, particularly for populations having a high prevalence of insulin resistance, such as the US population. If the US public were to modify its eating habits in the direction of better weight control and more exercise, higher intakes of carbohydrate might be better tolerated. At the same time, the experience with the Mediterranean population reveals that in healthier populations, diets relatively high in unsaturated fatty acids are well tolerated and are associated with a low prevalence of both coronary heart disease and type 2 diabetes.

Heterogeneity in adipose tissue metabolism: Causes, implications and management of regional adiposity

The observation that different patterns of adipose tissue distribution are associated with different metabolic abnormalities, has recently given new impetus to research in obesity. Due to several methodologic problems, however, many aspects of regional excess of adipose tissue are still poorly understood. Among them, the causes and the metabolic consequences of regional adiposity are particularly important. Heterogeneity in adipose tissue distribution may be determined by a combination of genetic and hormonal causes. Both factors may determine differences in metabolism of various adipose tissue compartments primarily by regulating LPL production, storage and release of triacylglycerols, and aromatization of androgens. Furthermore, changes in adipocyte sensitivity to hormones such as, sex steroids, glucocorticoids, insulin and adrenergic hormones may also regulate fat distribution in various adipose tissue compartments. The metabolic heterogeneity of adipose tissue from various compartments, particularly the differences between the portal and subcutaneous adipose tissues, may account for several metabolic abnormalities associated with upper body adiposity. However, no direct evidence is available to confirm this hypothesis. Recent advances in the methodology to study adipose tissue distribution (mainly CT and MRI) may provide the necessary tools to evaluate the true impact of adiposity in various compartments on intermediary metabolism and to identify a morbid adipose tissue compartment. These observations may help in designing better therapeutic strategies targeted towards regional adiposity and its metabolic complications.

Overweight and Sympathetic Overactivity in Black Americans

A large body of clinical investigation implicates an important role for the sympathetic nervous system in linking obesity with hypertension. However, the experimental support for this hypothesis is derived from strictly white cohorts. The goal of this study was to determine whether being overweight begets sympathetic overactivity in black Americans, the ethnic minority at highest risk for hypertension. We recorded postganglionic sympathetic nerve discharge with microelectrodes in muscle nerve fascicles of the peroneal nerve in 92 normotensive young adult black men and women within a wide range of body mass index. The same experiments were performed in a control group of 45 normotensive white men and women of similar ages and body mass indices. The major new findings are 2-fold. First, in young, normotensive, overtly healthy black women, being overweight begets sympathetic overactivity (r =0.45, P =0.0009), a putative intermediate phenotype for incident hypertension. Second, in black men, sympathetic nerve discharge is dissociated from body mass index (r =0.03, P =NS). This dissociation is explained in part by a 20% to 40% higher rate of sympathetic nerve discharge in lean black men compared with lean white men and lean black and white women (28±3 versus 18±2, 21±2, and 17±2 bursts/min, respectively;P <0.05). Sympathetic nerve discharge in lean black men is comparable to that of overweight black men and women as well as white men and women. These data provide the first microneurographic evidence for tonic central sympathetic overactivity in blacks, both adiposity-related sympathetic overactivity in black women and adiposity-independent sympathetic overactivity in black men.

Insulin Resistance and Obesity: The role of fat distribution pattern

O besity is often associated with chronic diseases such as NIDDM, atherosclerosis, and dyslipidemia (1-3). The mechanisms underlying these associations are still poorly understood. However, recent studies suggest that insulin resistance may play a key role in the pathophysiology of the metabolic abnormalities associated with obesity and its morbidity (4-7). In fact, insulin resistance is frequently observed in obese subjects and constitutes an independent risk factor for the development of NIDDM and atherosclerosis (4,5). Furthermore, more recent investigations have suggested that insulin resistance also has a role in the pathophysiology of dyslipidemia (6) and hypertension (7).