Normal-weight Control Subjects Research Articles

Visceral adipose tissue impairs insulin secretion and insulin sensitivity but not energy expenditure in obesity

In obesity, a central pattern of fat distribution is mostly associated with hyperinsulinemia, insulin resistance, and hyperlipemia, thus promoting the development of non-insulin-dependent diabetes mellitus and cardiovascular disease. In addition, in obesity, changes in energy expenditure are hypothesized to be involved in the development or maintenance of excessive body fat storage. In this study, abdominal fat distribution by computed tomographic (CT) scan was used to study the relation between the visceral fat depot, insulin secretion, and insulin sensitivity in a group of obese subjects with normal glucose tolerance (n = 26; body mass index [BMI], 39 ± 1 kg/m 2) and a group of normal-weight control subjects (n = 9; BMI, 23 ± 1 kg/m 2). The minimal model method was used to assess insulin sensitivity, S I, and first-phase (Φ1) and second-phase (Φ2) β-cell sensitivity from plasma glucose, insulin, and C-peptide concentrations measured during an intravenous glucose tolerance test ([IVGTT] 0.33 g/kg body weight). Moreover, we evaluated the relationships between these parameters and the resting metabolic rate (RMR) and glucose-induced thermogenesis (GIT) measured by indirect calorimetry. The data show the following: (1) in obese subjects, (Φ1) is greater but not statistically different from the value in control subjects (252 ± 41 v 157 ± 25 dimensionless 10 9); (2) Φ2 is significantly higher in obese subjects (27 ± 4 v 14 ± 2 min −1 × 10 9, P < .05), with a positive correlation between the amount of visceral adipose tissue (VAT) and Φ2 ( r = .49, P < .05); (3) S l is decreased in the obese group (2.8 ± 0.3 v 9.7 ± 1.6 10 −4 · min −1/(μU · mL −1), P < .0001), with a negative correlation of S l, with the adiposity index BMI ( r = −.67, P < .0001) and VAT ( r = −.56, P < .05); (4) RMR, expressed in absolute terms, was significantly increased in obese versus lean subjects (5.9 ± 0.2 v 4.6 ± 0.3 kJ/min, P < .01), whereas when RMR was adjusted for fat-free mass (FFM), the difference between the two groups disappeared (0.09 ± 0.003 v 0.09 ± 0.002 kJ/min · kg FFM). We did not observe any difference in GIT between lean and obese subjects. Moreover, GIT was significantly correlated with FFM ( r = .69, P < .005), but not with BMI. The amount of VAT did not correlate with RMR or GIT. In conclusion, these results suggest that in obese subjects with normal glucose tolerance, insulin sensitivity is impaired and the β-cell hyperresponse to glucose is mainly due to an enhanced second-phase β-cell secretion. The degree of visceral fat deposition seems to affect insulin secretion and worsens insulin sensitivity, but does not influence energy expenditure.

Plasma fibronectin in overweight men and women

When compared with 67 age- and sex-matched normal weight control subjects, the 71 overweight patients displayed obviously higher levels of plasma fibronectin. For a similar body mass index (BMI) the 16 overweight men younger than 45 years had a significantly (P < 0.01) higher plasma fibronectin level (455 +/- 99.3 mg/l; mean +/- SD) than the 16 age-matched overweight women (351 +/- 105 mg/l) while there was no significant difference between the 22 overweight men (446 +/- 89.2 mg/l) and the 17 overweight women (475 +/- 111 mg/l) older than 45 years. Particularly high plasma fibronectin levels were noted in the five women with upper body (android) obesity. Plasma fibronectin was positively correlated with BMI, serum triglyceride concentration, plasma fibrinogen and serum cholinesterase activity. It is considered that metabolic disturbances related to upper body obesity may lead to an enhanced hepatic secretion of VLDL and of several plasma proteins including fibronectin.

Insulin-induced decline of plasma amino acid concentrations in obese subjects with and without non-insulin-dependent diabetes

Obesity-associated hyperaminoacidemia is traditionally interpreted as a consequence of insulin resistance. We performed two different experiments to investigate the effects of both obesity-associated insulin resistance and the insulin resistance of non-insulin-dependent diabetes mellitus (NIDDM) on amino acid metabolism. In the first experiment, we measured postabsorptive amino acid concentrations and their decline in response to an oral carbohydrate load in 19 obese nondiabetic women and 19 normal-weight nondiabetic controls. Obese subjects were more resistant to insulin with respect to its effects on glucose metabolism than normal-weight controls, as calculated by the method described by Matthews. However, postabsorptive plasma concentrations of the so-called large neutral amino acids (LNAA), namely phenylalanine, tyrosine, valine, leucine, and isoleucine, and their decrease in response to carbohydrate consumption were similar in both groups. In the second experiment, we compared the decrease of plasma concentrations of LNAA during a euglycemic, hyperinsulinemic clamp in obese subjects with and without NIDDM. Peripheral glucose uptake (PGU) was more impaired in NIDDM subjects compared with obese controls. Furthermore, hepatic glucose production (HGP) was less attenuated by insulin infusion in NIDDM than in control subjects. Postabsorptive plasma LNAA concentrations were not different in the two groups. Values obtained in either group were not different from the postabsorptive concentrations in the normal-weight control subjects of experiment 1. All amino acid levels decreased substantially in response to insulin infusion. The magnitude of the decrease was not significantly different in the two groups, except for a slightly greater decrease of the plasma isoleucine concentration in obese control subjects. These results indicate that insulin resistance in obesity and NIDDM has dissociated effects on insulin-mediated glucose and amino acid metabolism. Although obese subjects both with and without NIDDM were resistant to insulin with respect to its effects on glucose metabolism, postabsorptive plasma levels of LNAA and their decrease in response to carbohydrate consumption or insulin infusion were similar in obese subjects, irrespective of the presence of NIDDM, and normal-weight control subjects.

Plasminogen activator inhibitor activity in various types of endogenous hypertriglyceridemia

In various groups of patients, plasminogen activator inhibitor (PAI), plasma insulin and triglyceride level are closely associated all together. To clarify this relationship we looked at PAI activity in patients with endogenous hypertriglyceridemia, 15 were obese (body mass index (BMI) higher than 27, mean: 36.2), 9 had a strictly normal weight (BMI lower than 25, mean: 22.8) and 11 had alcohol induced hypertriglyceridemia. They were compared to 20 control subjects of normal weight and with plasma triglyceride level lower than 1.7mmol/l and 11 hypercholesterolemic patients. Overall mean PAI levels in hypertriglyceridemic patients were higher than in controls and hypercholesterolemic subjects. Compared to controls (mean±SD PAI: 9.8±5AU/ml), both PAI activity (30±12U/ml p<0.05) and plasma insulin were elevated in obese hypertriglyceridemic patients but not different from normal in the normal weight hypertriglyceridemic patients (PAI activity 15.2±4.1 U/ml ns). In alcoholic hypertriglyceridemic patients, PAI activity was elevated (21±9.7U/ml p<0.05) but insulin was normal. In the whole series PAI activity was weekly correlated with triglyceride level (r=0.295 p<0.05), but in strong positive relationship with insulin levels (r=0.572 p<0.0001). These results suggest that in obese patients insulin resistance is the common cause of both hypertriglyceridemia and elevation of PAI activity. Other mechanisms have to be looked for in some conditions such as alcohol associated hypertriglyceridemia. Endogenous hypertriglyceridemia occurring in strictly normal weight subjects is not accompanied by elevated PAI levels.

Weight loss normalizes the inhibitory effect of N6-(phenylisopropyl)adenosine on lipolysis in fat cells of massively obese human subjects.

1. Fat cells were isolated from massively obese patients at or before gastric bypass, from other patients after normalization of body weight after gastric bypass or gastroplasty (post-bypass patients) and from control subjects of a stable normal body weight. 2. The inhibition of isoprenaline-stimulated lipolysis by N6-(phenylisopropyl)adenosine in the presence of adenosine deaminase was much attenuated in cells from the massively obese patients as compared with those from normal-weight control subjects, but was normal in cells from post-bypass patients. 3. Isolated fat cells of the massively obese patients were larger (913 +/- 197 pl, mean +/- SEM) than those of the normal-weight group (437 +/- 95 pl). The volume of cells from the post-bypass patients was only 125 +/- 49 pl, although the body mass index of this group was almost exactly the same as that of the normal-weight control subjects. 4. Although epidemiological studies have suggested that genetic factors are important in the development and maintenance of obesity, these results demonstrate that the changes observed in the inhibitory regulation of lipolysis in obesity are secondary.

Insulin resistance versus insulin secretion in the hypertension of obesity.

We measured the degree of association between obesity, blood pressure, insulin resistance, and insulin secretion in 72 male and female obese hypertensive, obese nonhypertensive, and normal weight control subjects. Baseline weight, body mass index, percent body fat, waist/hip ratio, and systolic and diastolic blood pressures were obtained. Insulin sensitivity was assessed according to Bergman's minimal model. Twelve-hour urinary c-peptide was measured after a standard liquid meal. Insulin action was inversely associated with blood pressure status, obesity status, and age. Meal-stimulated c-peptide excretion significantly correlated with systolic blood pressure and percent fat but not with body mass index or age. Multivariate regression analysis indicated that, of the measures of body composition, percent fat and waist/hip ratio had the strongest correlation with insulin action either alone or in combination with c-peptide excretion. Obese hypertensive patients had an index of insulin action (10(-4).min-1/[microunits/ml]) of 1.34 +/- 0.19, which was significantly (p less than 0.003) lower than in the obese nonhypertensive patients (index, 2.26 +/- 0.10) or the nonobese subjects (index, 5.41 +/- 0.26, p less than 0.001). Meal-stimulated c-peptide excretion (nmol/kg lean body mass) was increased only in the obese hypertensive group (0.32 +/- 0.01) and was significantly higher (p less than 0.001) than in the obese nonhypertensive (0.16 +/- 0.01) or the nonobese subjects (0.14 +/- 0.01). These results support the hypothesis that abnormalities in blood pressure regulation, insulin-stimulated glucose uptake, and insulin secretion coexist.

Study of Somatostatin in Simple Obesi y

C-peptide, as a marker for pancreatic beta cells function, and somatostatin (SS) in plasma of obese males (n = 15) and a corresponding normal-weight control subjects (n = 10) are studied in this work. Fasting plasma SS and serum C-peptide are significantly higher in obese vs lean group, this can be explained by hypertrophy of both D- and B-cells of the pancreatic islets reported by other investigators. Post-prandial plasma SS in insignificantly increased in obese vs the control group wheres the increase in C-peptide levels is significant suggesting unequal response of B- and D-cells to meal in the obese group. We concluded that circulating SS may play important role in development of obesity. Hyperinsulinaemia, documented in obesity may be due to hypersecretion of insulin (marked by rise of serum C-peptide in this work), and this may contribute to increased somatomedin-C in obesity.

Characteristics of psychomotor performance and time cognition in moderately obese patients.

To clarify adherence of obese subjects to external food-relevant stimuli, we examined time cognition and psychomotor functioning of the obese under noneating conditions in the present study. Matched on the basis of age, sex, height, intelligence quotient and education, 13 moderately, but adult-onset obese (mean obesity index +/- SEM, 53.9 +/- 5.0% by Matsuki's method) and 13 normal weight subjects (-6.3 +/- 2.3%) were tested. Obese females were slower than normal weight control subjects in alternate tapping of two metal plates (p less than 0.01) and in transfer of a dowel (p less than 0.05). Normal subjects were slightly but significantly (p less than 0.05) more efficient in a self-cued traverse movement test, whereas the obese subjects were very much less efficient in the self-cued than in the externally-cued test. These findings suggest that evaluation of deficits of the obese must consider other factors in addition to simple physical slowness due to fattening. In time cognition tests, cognitive levels of the obese were more accurate when initiated by time cues than when they were self-cued (p less than 0.01). The results indicate that obese (even after adult-onset) may exhibit impairment in internal time cognition when deprived of external modulating time cues.

Relationship between body weight and blood pressure and some metabolic parameters in psoriatic patients.

The relationship between body weight and blood pressure, total serum cholesterol, triglycerides, uric acid and glucose was investigated in 203 psoriatic patients in comparison with 904 healthy controls. In the psoriatic patients, these parameters were clearly related to their body weight. Those psoriatic patients of normal weight exhibited lower mean values of all the parameters compared with overweight psoriatic patients while they did not differ from control subjects of normal weight. Our results suggest that only overweight psoriatic patients exhibit the metabolic abnormalities frequently reported in the literature, while psoriatic patients of normal weight do not differ from the general population in this respect.

Obesity is associated with impaired insulin-mediated potassium uptake

The ability of insulin to promote extrarenal potassium uptake and to stimulate glucose uptake was examined in eight obese and ten normal weight control subjects. Insulin was infused at three rates to produced plasma insulin concentrations of approximately 100, 1,900, and 19,000 μU/mL. Insulin-mediated potassium, as well as glucose uptake, was diminished during the lowest dose insulin clamp study (100 μU/mL) but could be normalized at pharmacologic plasma insulin concentrations. These results indicate that obese subjects are resistant to the ability of insulin to stimulate potassium uptake by extrarenal tissues. Imparied potassium uptake at physiologic plasma insulin levels, with normalization at supraphysiologic insulin concentrations, is most consistent with a decrease in the number of insulin receptors on insulin target tissues.

Taste and eating disorders

Taste responses to sucrose and fat-containing stimuli were examined in a population of young women with eating disorders. Anorectic-restrictor and anorectic-bulimic patients were compared with normal-weight bulimic patients and with normal-weight control subjects. Sensory estimates of sweetness and fat content of 20 different mixtures of milk, cream, and sugar did not differ among subject groups. In contrast, relative preferences for sugar vs fat as determined by the Response Surface Method differed between patients with eating disorders and control subjects. Normal-weight bulimic patients preferred sweeter stimuli than did control subjects. Anorectic-restrictor and anorectic-bulimic patients liked sweet but disliked high-fat stimuli and showed elevated optimal sugar:fat (S:F) ratios. This pattern of response did not change following weight regain. The stability of preference profiles suggests that taste responsiveness may be independent of diagnostic categories, bulimic behaviors, or acute changes in body weight.

Effect of Age, Gender, and Obesity on Midazolam Kinetics

The effects of age, sex, and obesity on the kinetics of single intravenous (iv) and oral doses of midazolam were evaluated in healthy volunteers who received 2.5-5 mg of iv midazolam on one occasion and 5-10 mg orally on another. Kinetics were determined from multiple plasma midazolam concentrations measured during 24 h after dosage. Midazolam elimination half-life (t1/2) after iv dosage was significantly prolonged in elderly (aged 60-74 yr) versus young (24-33 yr) males (5.6 vs. 2.1 hours, P less than 0.01) and total clearance was significantly reduced (4.4 vs. 7.8 ml X min-1 X kg-1, P less than 0.01), leading to increased systemic availability of the oral dose (50% vs. 41%, P less than 0.05). However total volume of distribution calculated by the area method (Vd) (1.6 vs. 1.3 1/kg) and protein binding (3.5 vs. 3.4% unbound) did not differ between groups. Among women there were no significant differences between elderly (64-79 yr) and young (23-37 yr) volunteers in t1/2 (4.0 vs. 2.6 h), clearance (7.5 vs. 9.4 ml X min-1 X kg-1), Vd (2.1 vs. 2.0 1/kg), protein binding (3.7% vs. 3.7% unbound), or oral bioavailability (38% vs. 36%). In obese volunteers (mean weight 117 kg; 173% of ideal weight) versus control subjects of normal weight (66 kg, 95% of ideal weight) matched for age, sex, and smoking habits, midazolam Vd was increased significantly (311 vs. 114 1, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Disparity between glucose-dependent insulinotropic polypeptide and insulin responses in obese man.

Studies were carried out in 32 obese patients and 30 normal-weight control subjects to ascertain the response of glucose-dependent insulinotropic polypeptide (GIP) and insulin to (1) oral and intravenous glucose (10 obese and 10 control subjects), (2) oral fat and intravenous glucose (eight obese and six control subjects) and (3) mixed test meal (14 obese and 14 control subjects). Basal mean insulin was higher in the obese (99 pmol/l) than in the control group (40 pmol/l), but fasting blood glucose and GIP were not significantly different from normal. The total integrated response of insulin in obese subjects after oral glucose was 54.1 versus 33.3 nmol . l-1 . h-1 in control subjects; glucose and GIP responses were similar in both groups. After intravenous glucose the integrated insulin response was 8.8 in the obese versus 5.0 nmol . l-1 . h-1 in control subjects; GIP was unaffected by intravenous glucose and glucose levels were similar. Following oral fat and intravenous glucose, insulin secretion was again abnormal in the obese, 24.5 versus 7.3 nmol . l-1 . h-1 in controls, but GIP responses were normal. However, the control subjects became hypoglycaemic after this test: blood glucose 2.8 mmol/l at 150 min compared with 4.6 mmol/l in the obese group. The insulin response to a mixed meal was also abnormal in obesity.

Short-term effects of a high-fiber, high-carbohydrate diet in very obese diabetic individuals.

The short-term effects of a weight-maintenance diet high in fiber and carbohydrate (HFHC) was studied in seven very obese individuals with type II diabetes mellitus. Such diets contained 68% of kcal as carbohydrate and total fiber content of 81 g (in contrast to 42% and 28 g during baseline). Fasting glucose concentrations, summed glucose concentrations, and 24-h glucosuria were unaffected in six of seven individuals. Fasting insulin levels decreased (-6.0 +/- 2.0 microU/ml, P less than 0.05), but meal-stimulated insulin concentrations were not altered. Triglyceride and HDL cholesterol concentrations were also unaffected. Total cholesterol concentrations fell in four individuals whose initial values exceeded 200 mg/dl. Basal glucose production rates were similar in the obese diabetic subjects, in five nonobese normal subjects, and in one obese normal individual (2.05 +/- 0.19 versus 2.63 +/- 0.30 and 1.85 mg/kg/min for the obese normal individual) while on baseline diets, and did not change with HFHC. During isoglycemic hyperinsulinemic glucose clamp procedures (maintenance of basal glucose concentrations), 40 mU/m2/min was infused intravenously for 2 h. Glucose disappearance rates increased significantly in the normal-weight control subjects, but did not increase during baseline diets in the obese type II diabetic subjects (4.65 +/- 0.80 versus 0.68 +/- 0.40 mg/kg/min). HFHC diet had no effect on glucose disappearance rates. Plasma insulin levels were 131.0 +/- 11.0, 120.0 +/- 11.0, and 120.0 +/- 5.0 microU/ml during these studies. These studies indicate that short-term HFHC diets without caloric restriction were ineffective in improving glycemic control or lessening insulin resistance in very obese patients with type II diabetes.

Increased plasma antithrombin III level in hyperlipidemic subjects

When compared to values obtained in healthy normolipidemic normal weight control subjects, the plasma antithrombin III level determined by immunological, clotting and thrombin-agarose diffusion techniques was found to be obviously decreased in patients with decompensated cirrhosis of the liver and slightly but significantly increased in hyperlipidemic and especially in hypertriglyceridemic subjects. Plasma antithrombin III was positively correlated with serum cholesterol level, the logarithm of serum triglyceride concentration and serum pseudocholinesterase activity. A weaker correlation between plasma fibrinogen and antithrombin III was noted in the investigated clinical material. It is suggested that the accelerated fatty acid and lipoprotein turnover occurring in many subjects with type IIb and type IV hyperlipoproteinemia might be accompanied by an enhanced hepatic protein synthesis involving various liver secretion enzymes and clotting factors as well as antithrombin III.

Pregnancy in the underweight woman: Course, outcome, and growth patterns of the infant

The obstetric performance and pregnancy outcome of 354 underweight patients were compared with matched control subjects of normal weight. The growth patterns of their infants were also compared. The underweight women had significantly higher rates of cardiac/respiratory problems, anemia, PROM, and endometritis but were less prone to develop pre-eclampsia. Prematurity and low Apgar scores were significantly more frequent in the infants of underweight women. There was no difference in the frequency of IUGR and in perinatal mortality rates. The mean birth weight of the infants of underweight women was 231 grams less than that of infants of control subjects. Underweight women, particularly if they were anemic, had a higher incidence of low-birth-weight infants despite adequate weight gain. AGA infants of underweight women were more likely to be below the twenty-fifth percentile for weight correlated with length by 12 months of age.

Food deprivation-induced activity in dietary obese, dietary lean, and normal-weight rats

Dietary obesity and dietary leanness were produced in adult male rats by feeding them either an assortment of palatable foods, or an unpalatable quinine-adulterated diet. When deprived of food the dietary obese rats initially showed little change in wheel running activity but as their weight fell to below normal levels they displayed a terminal burst of activity similar to that seen in normal-weight control subjects. Dietary lean rats, on the other hand, increased their wheel running activity at an accelerated rate, relative to normal-weight controls, when food deprived. Expressing the activity data as a function of percentage normal body weight eliminated these group differences. The results demonstrate that body weight must fall to some relatively fixed, i.e., diet independent, critical level before activity increases during a fast. Therefore, as measured by deprivation-induced activity, dietary obese, dietary lean, and normal-weight rats do not equally defend their particular weight levels.

Effect of malnutrition on the metabolism of sex hormones in man.

The effects of caloric deprivation and accompanying body weight loss on gonadal hormone metabolism were studied in young women with anorexia nervosa. In these patients serving as models of uncomplicated malnutrition, the biotransformation of labeled testosterone and estradiol was followed after intravenous injection of these hormones. The metabolite distribution pattern is affected by thyroid status. All of 8 anorexia nervosa patients in whom testosterone metabolism was studied had low plasma Ta and borderline T4 levels, along with substantial deviation from normal body weight. The androsterone to etiocholanolone (A/E) ratio was greatly diminished, precisely as expected from a hypothyroid state, although these patients, lacking classic symptomatology, were not hypothyroid. Three of these patients restudied after administration of T3 showed a reversal of direction of testosterone metabolism, i.e., more than a doubling of the 5a to 5β ratio. During spontaneous remission from the disease and progressive weight gain, the plasma T3 rose and the AlE ratio increased. In 7 patients with anorexia nervosa, the metabolism of estradiol was compared with that of normal weight control subjects and of 4 obese patients. In the malnourished patients the formation of 2‐hydroxyestrone was markedly greater than in the other 2 groups, while estriol production was significantly diminished. In the obese subjects estriol formation increased and catecholestrogen production decreased. These opposite trends in anorexic and obese patients suggest that the metabolic alteration of estradiol is a consequence of low body weight and food intake and not the result of other factors specific to anorexia nervosa. It is concluded that the changed estradiol metabolism in anorexia nervosa is not the result of the thyroid status in these subjects, and it is speculated that the distortion of estradiol metabolism is attenuated by the biochemical hypothyroidism accompanying malnutrition. This results in a diminution of estrogenic activity of the endogenous estradiol which may accentuate the consequences of the decreased production of the hormone in this disease.

Obesity, hyperinsulinism, and diabetes mellitus in childhood

Plasma glucose, immunoreactive insulin, and growth hormone following oral glucose were compared in 42 obese and 30 normal-weight children. Twelve (28 per cent) of the obese children had chemical diabetes, and a further 11 (26 per cent) had significant impairment of mean carbohydrate tolerance. All but the youngest exhibited hyperinsulinemia. There was no clear division between normal and abnormal carbohydrate tolerance or insulin response in the obese children, but there was a general tendency toward increasing hyperinsulinemia and decreasing carbohydrate tolerance with age and duration of obesity. Age of onset or degree of obesity did not relate to carbohydrate intolerance, and hyperinsulinemia did not relate to a family history of diabetes. Significant carbohydrate intolerance was seen only in association with a delay in the attainment of peak insulin concentration. Growth hormone was lower in the obese children than in the normal-weight control subjects, but the rise during the latter part of the glucose tolerance test was significantly greater in the obese children with chemical diabetes than in those with normal carbohydrate tolerance.

Effect of protein meals on plasma insulin in mildly diabetic patients.

We have reported that in mildly diabetic patients increases in plasma insulin are subnormal in response to infused amino acids while others have reported excessive increases in response to ingested protein. Increases in plasma insulin exhibited by nonobese, mildly diabetic patients in response to the ingest ion of protein meals and to the intravenous administration of a mixture of ten essential amino acids were compared to those of healthy nonobese control subjects. The plasma insulin responses to protein meals were also determined in a group of mildly obese, mildly diabetic patients. The results of these studies indicate that: (1) the mean insulin response of nonobese mildly diabetic patients to protein meals is subnormal and not excessive, (2) mildly obese, mildly diabetic patients respond excessively to protein meals as compared to control subjects of normal weight, and (3) the excessiye insulin response to protein meals reported by others to occur in diabetics is probably the result of a greater degree of adiposity in their diabetics than in their control subjects, rather than of the presence of diabetes mellitus. Unless the degree of adiposity is similar in diabetic and healthy subjects, meaningful comparison of their insulin responses to protein meals or other stimuli cannot be made.