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Biomedical subjects

L Groop

Publications and source records attributed to L Groop.

At least 127 records · Page 7Linked to original sources
PubMed1992

Insulin resistance in type 2 (non-insulin-dependent) diabetic patients with hypertriglyceridaemia.

Hypertriglyceridaemia, which is frequently seen in Type 2 (non-insulin-dependent) diabetes mellitus, is associated with insulin resistance. The connection between hypertriglyceridaemia and insulin resistance is not clear, but could be due to substrate competition between glucose and lipids. To address this question we measured glucose and lipid metabolism in 39 Type 2 diabetic patients with hypertriglyceridaemia, i.e. mean fasting serum triglyceride level equal to or above 2 mmol/l (age 59 +/- 1 years, BMI 27.4 +/- 0.5 kg/m2, HbA1c 8.0 +/- 0.2%, serum triglycerides 3.2 +/- 0.2 mmol/l) and 41 Type 2 diabetic patients with normotriglyceridaemia, i.e. mean fasting serum triglyceride level below 2 mmol/l (age 58 +/- 1 years, BMI 27.0 +/- 0.7 kg/m2, HbA1c 7.8 +/- 0.2%, serum triglycerides 1.4 +/- 0.1 mmol/l). Insulin sensitivity was assessed using a 340 pmol.(m2)-1 x min-1 euglycaemic insulin clamp. Substrate oxidation rates were measured with indirect calorimetry and hepatic glucose production was estimated using a primed (25 microCi)-constant (0.25 microCi/min) infusion of [3-3H]-glucose. Suppression of lipid oxidation by insulin was impaired in patients with hypertriglyceridaemia vs patients with normal triglyceride levels (3.5 +/- 0.2 vs 3.0 +/- 0.2 mumol.kg-1 x min-1; p < 0.05). Stimulation of glucose disposal by insulin was reduced in hypertriglyceridaemic vs normotriglyceridaemic patients (27.0 +/- 1.3 vs 31.9 +/- 1.6 mumol.kg-1 x min-1; p < 0.05) primarily due to impaired glucose storage (9.8 +/- 1.0 vs 14.6 +/- 1.4 mumol.kg-1 x min-1; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1992

Factors associated with basal metabolic rate in patients with type 2 (non-insulin-dependent) diabetes mellitus.

To examine determinants of basal metabolic rate we studied 66 Type 2 (non-insulin-dependent) diabetic and 24 healthy age- and weight-matched control subjects with indirect calorimetry and infusion of [3H-3-] glucose. Eight Type 2 diabetic patients were re-studied after a period of insulin therapy. Basal metabolic rate was higher in Type 2 diabetic patients than in control subjects (102.8 +/- 1.9 J.kg LBM-1.min-1 vs 90.7 +/- 2.8 J.kg LBM-1.min-1; p less than 0.01) and decreased significantly with insulin therapy (p less than 0.01). The basal rate of hepatic glucose production was higher in Type 2 diabetic patients than in control subjects (1044.0 +/- 29.9 vs 789.3 +/- 41.7 mumol/min; p less than 0.001) and decreased after insulin therapy (p less than 0.01). Hepatic glucose production correlated positively with basal metabolic rate both in Type 2 diabetic patients (r = 0.49; p less than 0.001) and in control subjects (r = 0.50; p less than 0.05). Lipid oxidation was increased in Type 2 diabetic patients compared with control subjects (1.68 +/- 0.05 vs 1.37 +/- 0.08 mumol.kg LBM-1.min-1; p less than 0.01) and decreased significantly after insulin therapy (p less than 0.05). The rate of lipid oxidation correlated positively with basal metabolic rate both in Type 2 diabetic patients (r = 0.36; p less than 0.01) and in control subjects (r = 0.51; p less than 0.01). These data demonstrate that basal metabolic rate, rates of hepatic glucose production and lipid oxidation are interrelated in Type 2 diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Effects of weight loss on substrate oxidation, energy expenditure, and insulin sensitivity in obese individuals.

To evaluate the effect of weight loss on substrate oxidation, energy expenditure, and insulin sensitivity we studied 12 obese subjects (body mass index 33.4 +/- 1.1) before and after 6 wk of a very-low-calorie diet (VLCD) with euglycemic insulin clamp in combination with indirect calorimetry. Body weight decreased from 105.3 +/- 4.6 to 94.1 +/- 4.0 kg (P less than 0.001) and fat mass from 47.2 +/- 3.6 to 37.7 +/- 3.0 kg (P less than 0.001). Total glucose disposal during insulin clamp increased from 30.4 +/- 4.3 to 38.4 +/- 4.4 mumol.kg lean body mass (LBM)-1.min-1 (P less than 0.05), insulin-stimulated glucose oxidation from 14.3 +/- 4.6 to 19.1 +/- 1.4 mumol.kg LBM-1.min-1 (P less than 0.05), and non-oxidative glucose metabolism from 16.0 +/- 3.8 to 19.3 +/- 3.6 mumol.kg LBM-1.min-1 (NS). Lipid oxidation decreased in the basal state (P less than 0.05) and during the insulin clamp (P less than 0.01). The basal rate of energy expenditure decreased from 99.1 +/- 4.6 to 88.5 +/- 2.7 kJ.kg LBM-1.min-1 (P less than 0.05) after weight reduction. A reduction in fat mass achieved by VLCD is associated with reduced lipid oxidation and, because of substrate competition, enhanced glucose oxidation. The physiological consequence is improved insulin sensitivity.

Adult↗
PubMed1992

Weight loss by very-low-calorie diets: effects on substrate oxidation, energy expenditure, and insulin sensitivity in obese subjects.

Weight reduction improves glucose utilization, but it is not known whether this occurs primarily through the oxidative or nonoxidative pathways of glucose metabolism. We studied this question in 12 obese subjects [whose body mass index (BMI) was 33.4 +/- 1.1 kg/m2)] before and after 6 wk on a very-low-calorie diet of 1680 kJ/d with the euglycemic insulin clamp technique in combination with indirect calorimetry. The mean body weight decreased from 105.3 +/- 4.6 to 94.1 +/- 4.0 kg (P less than 0.001). This was mainly due to a reduction in fat mass from 47.2 +/- 3.6 to 37.7 +/- 3.0 kg (P less than 0.001), whereas lean body mass decreased only slightly (from 58.0 +/- 2.0 to 56.4 +/- 1.8 kg). The basal energy expenditure decreased with weight loss by 10.7%. This was associated with a reduced rate of lipid oxidation (P less than 0.05). Weight loss increased glucose utilization by 26%, primarily by enhancing insulin-stimulated glucose oxidation (P less than 0.05), whereas the effect on nonoxidative glucose metabolism was less pronounced (P greater than 0.05). Substantial weight loss increases glucose utilization by enhancing glucose oxidation.

Adult↗
PubMed1992

Metabolic control and progression of complications in insulin-dependent diabetic patients after kidney transplantation.

Patient survival and progression of complications were monitored for 3 years after kidney transplantation in 29 type-1 diabetic patients. Ten age-matched, non-diabetic kidney-transplanted patients served as controls. Five diabetic patients died during follow-up (three cardiovascular events, two infections), three diabetic patients had a non-fatal myocardial infarction and four developed cerebrovascular complications after transplantation. Of the diabetic patients, 69% suffered from proliferative retinopathy before transplantation; 20% of them improved, 65% remained unchanged and 15% deteriorated after transplantation. Motor but not sensory conduction velocity measured from the nervus medianus improved after transplantation. Autonomic neuropathy was observed in 50% of the patients and was unaffected by transplantation. Glycaemic control did not improve significantly during follow-up (HbA1, 10.6 +/- 0.5% before and 9.5 +/- 0.6% 3 years after transplantation). Body weight increased in both diabetic and non-diabetic patients within 3 years after transplantation (from 68 +/- 2 to 77 +/- 6 kg in diabetics, P less than 0.01; from 167 +/- 4 to 77 +/- 6 kg in non-diabetics, P less than 0.01). Subcutaneous fat thickness measured from computer tomography scans of the calf increased in diabetic patients from 5.0 +/- 0.6 to 6.1 +/- 0.9 mm (P less than 0.05). However, the cross-sectional areas of triceps and calf muscles did not increase, suggesting that the increase in body weight was solely due to an increase in fat. It is clear that diabetes-related complications continue to progress and are not influenced by a successful kidney transplant.

Adult↗
PubMed1992

Pancreatic surgery, not pancreatitis, is the primary cause of diabetes after acute fulminant pancreatitis.

Acute fulminant pancreatitis is associated with significant morbidity and mortality. To examine the outcome of conservative and surgical treatment of this disorder, 36 patients who survived an initial episode were restudied after a mean of six years. Fifty three per cent had developed diabetes mellitus, half of whom required insulin therapy. Pancreatic resection was associated with a 100% frequency of diabetes, while only 26% of those treated with peritoneal lavage developed this (p less than 0.001). Insulin secretion and sensitivity were assessed using the hyperglycaemic glucose clamp technique. First phase insulin secretion was impaired in surgically treated patients (mean (SEM) 14 (5) microU/ml x 10 minutes) compared with conservatively treated patients and control subjects (144 (66) and 87 (12) microU/ml x 10 minutes, respectively; p less than 0.05). Second phase and 'maximal' insulin secretion were also impaired among the surgically treated patients compared with the conservatively treated patients and the controls. Insulin sensitivity was reduced among the surgically treated patients (2.88 (58) mg/kg.minute) when compared with conservatively treated patients and healthy control subjects (5.87 (1.02) and 6.45 (0.66) mg/kg.minute; p less than 0.05). Pancreatic resection is associated with a very high frequency of diabetes compared with peritoneal lavage, and these results favour conservative treatment of active fulminant pancreatitis whenever possible.

Acute Disease↗
PubMed1992

Effect of gender on insulin resistance associated with aging.

To examine whether age-related changes in energy metabolism are influenced by gender, 20 females and 20 males varying in age from 21 to 80 yr were studied with euglycemic insulin clamp in combination with indirect calorimetry and infusion of [3-3H]glucose. Lean body mass (LBM) was measured with the tritiated water technique. Fat percentage correlated with age in males (r = 0.60; P < 0.05) but not in females. Although the rates of insulin-stimulated total glucose disposal and nonoxidative glucose metabolism were similar in females and males, nonoxidative glucose metabolism expressed per kilogram body weight (r = -0.64; P < 0.01) or per kilogram LBM (r = -0.46; P < 0.05) was inversely correlated with age only in males. Basal metabolic rate expressed per kilogram body weight decreased with age in both sexes, but no correlation with age was observed when data were expressed per kilogram LBM. The data clearly demonstrate different effects of age on energy metabolism in males and females.

Adult↗
PubMed1991

Modulation of hepatic glucose production by non-esterified fatty acids in type 2 (non-insulin-dependent) diabetes mellitus.

To study the effect of changes in plasma non-esterified fatty acid concentration on suppression of hepatic glucose production by insulin eight Type 2 (non-insulin-dependent) diabetic patients participated in three euglycaemic, hyperinsulinaemic (108pmol.m2-1.min-1) clamp studies combined with indirect calorimetry and infusion of [3-3H]-glucose and [1-14C]palmitate; (1) a control experiment with infusion of NaCl 154 mmol/l, (2) heparin was infused together with insulin, and (3) an antilipolytic agent, Acipimox, was administered at the beginning of the experiment. Six healthy volunteers participated in the control experiment. Plasma non-esterified fatty acid concentrations during the insulin clamp were in diabetic patients: (1) 151 +/- 36 mumol/l, (2) 949 +/- 178 mumol/l, and (3) 65 +/- 9 mumol/l; in healthy control subjects 93 +/- 13 mumol/l. Non-esterified fatty acid transport rate, oxidation and non-oxidative metabolism were significantly higher during the heparin than during the Acipimox experiment (p less than 0.001). Suppression of hepatic glucose production by insulin was impaired in the diabetic compared to control subjects (255 +/- 42 vs 51 +/- 29 mumol/min, p less than 0.01). Infusion of heparin did not affect the suppression of hepatic glucose production by insulin (231 +/- 49 mumol/min), whereas Acipimox significantly enhanced the suppression (21 +/- 53 mumol/min, p less than 0.001 vs 154 mmol/l NaCl experiment). We conclude that insulin-mediated suppression of hepatic glucose production is not affected by increased non-esterified fatty acid availability. In contrast, decreased non-esterified fatty acid availability enhances the suppression of hepatic glucose production by insulin.

Administration, Oral↗
PubMed1991

Non-esterified fatty acids do not contribute to insulin resistance in persons at increased risk of developing type 2 (non-insulin-dependent) diabetes mellitus.

The mechanisms underlying insulin resistance in Type 2 (non-insulin-dependent) diabetes mellitus are not fully understood. An enhanced lipid/non-esterified fatty acid oxidation could provide an explanation. To test this hypothesis we examined the relationship between glucose and lipid metabolism in 44 first-degree relatives (28 glucose-tolerant and 16 glucose-intolerant) of Type 2 diabetic patients and in 18 healthy control subjects. Total body glucose disposal was impaired among both glucose-tolerant and glucose-intolerant relatives compared with control subjects (36.3 +/- 3.8 and 30.4 +/- 2.7 vs 47.7 +/- 3.4 mumol.kgLBM-1. min-1; p less than 0.05). The impairment in glucose disposal among the relatives was primarily accounted for by impaired non-oxidative glucose metabolism (14.8 +/- 3.0 and 12.5 +/- 1.8 vs 25.3 +/- 3.1 mumol.kgLBM-1.min-1; p less than 0.05). Plasma non-esterified fatty acid concentrations were similar in both glucose-tolerant and glucose-intolerant relatives and control subjects (646 +/- 36, 649 +/- 43 and 615 +/- 41 mumol/l) and showed the same degree of suppression by insulin (99 +/- 8, 86 +/- 7 and 84 +/- 9 mumol/l). Basal lipid oxidation was similar in all groups (1.29 +/- 0.09, 1.52 +/- 0.13 and 1.49 +/- 0.21 mumol.kgLBM-1. min-1). Furthermore, insulin suppressed lipid oxidation to the same degree in glucose-tolerant, glucose-intolerant relatives and control subjects (0.65 +/- 0.13, 0.88 +/- 0.15 and 0.59 +/- 0.09 mumol.kgLBM-1.min-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Basal Metabolism↗
PubMed1991

Fuel metabolism in anorexia nervosa and simple obesity.

To examine insulin sensitivity and the relative contribution of different fuels to energy metabolism in anorexia nervosa and obesity, we measured oxidation (indirect calorimetry) of glucose, lipids, and proteins in the basal state and during an insulin clamp (+45 mU/m2.min) in 11 women with anorexia nervosa (age, 25 +/- 3 years; body mass index [BMI], 13.6 +/- 0.4 kg/m2; fat mass, 15.7% +/- 1.6%), eight obese women (age, 31 +/- 3; BMI 36.0 +/- 1.5; fat mass, 47.1% +/- 1.9%), and eight controls (age, 26 +/- 3; BMI, 21.8 +/- 0.9; fat mass, 25.7% +/- 3.6%). Expressed per lean body mass, (LBM), glucose disposal was equally reduced in anorectics (7.53 +/- 0.62 mg/kg LBM.min) and obese (6.80 +/- 1.07 mg/kg LBM.min) compared with controls (10.64 +/- 0.69 mg/kg LBM.min; P less than .01). The reduction in glucose disposal in anorectics was primarily due to a significant (P less than .01) reduction in glucose storage, while glucose oxidation was normal. In obese women, both storage and oxidation of glucose were reduced compared with controls (P less than .01). Basal energy expenditure was similar in anorectic, obese, and control subjects (20.6 +/- 1.00, 23.7 +/- 0.56, 23.2 +/- 1.36 cal/kg LBM.min, respectively). However, the contribution of glucose, lipids, and proteins to basal energy expenditure differed between anorectic (62%, 16%, 22%), obese (26%, 58%, 16%), and control (30%, 54%, 16%) subjects (P less than .05 v all). In conclusion, in anorexia nervosa, insulin stimulates glucose oxidation more than storage. In obesity, both components of insulin-stimulated glucose metabolism are impaired.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Demonstration of a novel feedback mechanism between FFA oxidation from intracellular and intravascular sources.

We examined the regulation of intracellular and intravascular lipolysis in vivo. In the first series of studies, plasma free fatty acids (FFA) were elevated moderately by heparin (plus approximately 600 mumol/l) in patients with non-insulin-dependent diabetes mellitus (NIDDM) and in normal subjects. The increase in plasma FFA increased plasma FFA oxidation "submaximally" (plasma FFA oxidation less than 100% of total lipid oxidation) in a plasma FFA concentration-dependent manner. The increase in plasma FFA oxidation significantly suppressed direct intracellular oxidation of FFA. In another group of patients with NIDDM, plasma FFA was markedly increased (plus approximately 1,500 mumol/l). Plasma FFA oxidation now accounted for all lipid oxidation. Compared with substrate oxidation rates observed at submaximally elevated plasma FFAs in the same subjects at similar insulin concentrations, total lipid oxidation increased, carbohydrate oxidation decreased, and total energy production increased. These data demonstrate the existence of an FFA-dependent insulin-independent feedback mechanism between FFA oxidation from intracellular and intravascular sources. Thus the preferred response of body tissues to a change in plasma FFA oxidation is a reciprocal change in direct intracellular FFA oxidation. Substrate competition between carbohydrate and lipid, as proposed by P. J. Randle et al. (Lancet 1:785, 1963), becomes operative after the capacity for regulation within components of lipid oxidation has been utilized.

Blood Glucose↗
PubMed1991

Treatment strategies for secondary sulfonylurea failure. Should we start insulin or add metformin? Is there a place for intermittent insulin therapy?

UNLABELLED: Which therapy should be used in non-insulin dependent diabetes mellitus (NIDDM) with secondary sulfonylurea failure? Should we start insulin therapy, try a period of intensified insulin therapy and then switch back to sulfonylurea or should we add metformin therapy? To address this question, we have compared these three treatment strategies in 36 NIDDM patients who failed on treatment with sulfonylureas during a 6 month period. Insulin (short and intermediate-acting insulin before breakfast and dinner) and the combination of 21 mg of glibenclamide and 1.5 g of metformin resulted in an equivalent 30% improvement in glycemic control without significant effects on lipids. Intensified insulin therapy (6 weeks of intermediate and short-acting insulin 3 times daily), on the other hand, initially lowered blood glucose to the same degree as during the other two treatment regimes, but after switching back to sulfonylurea therapy (21 mg of glibenclamide/day) blood glucose concentrations returned to pretreatment values. Insulin therapy resulted in a 5 kg increase in body weight, 63% of which was accounted for by an increase in fat mass. Although body weight was unchanged during glibenclamide/sulfonylurea therapy, lean body mass and energy expenditure decreased significantly (p less than 0.05). Body weight and energy metabolism remained unchanged during intermittent insulin therapy. CONCLUSIONS: Despite similar blood glucose lowering properties, insulin and the combination of sulfonylurea and metformin have different effects on energy metabolism and body composition. Since these effects were not observed during treatment with sulfonylurea alone, they must be ascribed to metformin.

Body Composition↗
PubMed1990

Obesity and insulin resistance in humans: a dose-response study.

Insulin-mediated glucose metabolism (euglycemic insulin clamp at plasma insulin concentration of 100 microU/mL) and glucose-stimulated insulin secretion (hyperglycemic clamp) were examined in 42 obese subjects (ideal body weight [IBW], 158 +/- 4%) with normal glucose tolerance and in 36 normal weight (IBW, 102% +/- 1%) age-matched controls. In 10 obese and eight control subjects, insulin was infused at six rates to increase plasma insulin concentration by approximately 10, 20, 40, 80, 2,000, and 20,000 microU/mL. Throughout the physiologic range of plasma insulin concentrations, both the increase in total body glucose uptake and the suppression of hepatic glucose production (HGP) were significantly impaired in the obese group (P less than .001 to .01). At the two highest plasma insulin concentrations, inhibition of HGP and the stimulation of glucose disposal were similar in both the obese and control groups. Insulin secretion during the hyperglycemic (+/- 125 mg/dL) clamp was twofold greater in obese subjects than in controls (P less than .01) and was inversely related to the rate of glucose uptake during the insulin clamp (r = -.438, P less than .05), but was still unable to normalize glucose disposal (P less than .05). In conclusion, our results indicate that insulin resistance is a common accompaniment of obesity and can be overcome at supraphysiological insulin concentrations. Both in the basal state and following a hyperglycemic stimulus obese people display hyperinsulinemia, which correlates with the degree of insulin resistance. However, endogenous hyperinsulinemia fails to fully compensate for the insulin resistance.

Adult↗
PubMed1990

Urinary excretion of kappa light chains in patients with diabetes mellitus.

The urinary excretion of kappa light chains, beta 2-microglobulin and albumin was examined in patients with newly diagnosed and long-standing insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus, and compared to age-matched control subjects. Patients with IDDM diagnosed within two months, presented with normal albumin excretion, whereas the concentrations of beta 2-microglobulin and kappa light chain in urine were higher than in control subjects. The initiation of insulin therapy reduced, but did not completely normalize, the elevated rate of kappa light chain excretion. Patients with IDDM of long duration showed increased urine excretion of kappa light chains and albumin. In keeping with the findings in IDDM, patients with newly diagnosed NIDDM (within one year) showed increased urinary excretion of kappa light chains compared with control subjects. There was, however, no further increase in light chain excretion with longer duration of NIDDM. To study the effect of short-term hyperglycemia on urinary protein excretion, 12 normal subjects participated in a three-step hyperglycemic clamp study, during which their plasma glucose concentration was raised by +50, +125 and +300 mg/dl. The urine excretion of albumin and beta 2-microglobulin rose progressively with each hyperglycemic clamp step, whereas that of kappa light chain excretion was unaffected by hyperglycemia. We conclude that increased urinary excretion of kappa light chain is a consistent finding in all types of diabetes mellitus, and can be observed even when the albumin excretion is normal. Since the serum concentration of kappa light chain is normal in diabetes, the increased urinary excretion of kappa light chains must be of renal origin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

The effect of exercise on urinary excretion of different size proteins in patients with insulin-dependent diabetes mellitus.

To examine whether exercise-induced proteinuria in diabetes is dependent upon the size of the excreted protein, we measured urinary excretion of beta 2-microglobulin, kappa light chains, albumin and IgG before and after 20 min of moderate ergometer exercise in 34 patients with insulin dependent diabetes mellitus (IDDM) and in eight healthy control subjects. Seventeen patients with newly diagnosed IDDM and 17 patients (seven of which had elevated albumin excretion rate) with longstanding IDDM were studied. Exercise did not significantly influence protein excretion in control and newly diagnosed IDDM subjects. In contrast, exercise enhanced excretion of beta 2-microglobulin (p less than 0.05-0.01), kappa light chains (p less than 0.001), albumin (p less than 0.005-0.001) and IgG (p less than 0.01-0.001) in patients with long-standing IDDM independently of whether the patient had proteinuria in the resting state or not. In conclusion, proteinuria induced by moderate exercise is not observed in the early stages of IDDM, and is independent of the size of the excreted protein. Therefore, moderate exercise does not appear to influence the size selectivity of the glomerular capillary wall in patients with longstanding IDDM.

Adult↗