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A Vaag

Publications and source records attributed to A Vaag.

At least 55 records · Page 3Linked to original sources
PubMed1995

Proinsulin immunoreactivity in identical twins discordant for noninsulin-dependent diabetes mellitus.

Disproportionate elevation [increased proinsulin/insulin (PI/INS) ratio] of PI immunoreactivity is associated with noninsulin-dependent diabetes mellitus (NIDDM). The nature of this abnormality is not known. To address the question of whether genetic factors contribute to hyperproinsulinemia, we measured fasting levels of PI immunoreactivity, intact INS, and C peptide (CP) in 12 pairs of monozygotic twins discordant for NIDDM for a mean (+/- SEM) period of 9 +/- 3 yr. Thirteen age- and body mass index-matched healthy subjects without any family history of NIDDM acted as controls. The nondiabetic twins had levels of fasting INS, CP, PI, PI/CP, and PI/INS similar to those of control subjects. Fasting levels of PI, and PI/CP and PI/INS ratios were significantly 2- to 3-fold elevated in NIDDM twins compared to those in both nondiabetic twins and control subjects. To investigate whether hyperproinsulinemia in these NIDDM patients was due to a differential elevation of intact PI or conversion intermediates, we analyzed PI profiles in NIDDM twins and normal subjects by high pressure liquid chromatography. PI was heterogeneous and consisted mainly of des(31,32)-PI and intact PI in both NIDDM patients and normal subjects, with no major difference in composition between the groups. Small amounts of des(64,65)-PI (0-11%) were measured in some patients and normal subjects. The results suggest that hyperproinsulinemia is not a genetically determined trait per se in NIDDM. Disproportionately elevated PI levels seem to be related to the actual disease process. Further conversion of intact PI and des(31,32)-PI may be equally impaired in NIDDM.

Adult↗
PubMed1994

Insulin resistance as the major cause of impaired glucose tolerance: a self-fulfilling prophesy?

Non-insulin-dependent diabetes (NIDDM) is a heterogeneous state involving various degrees of beta-cell dysfunction and insulin resistance, although the relative importance of these two factors is controversial. Several single gene disorders of carbohydrate metabolism have their main pathophysiological defect largely restricted to the beta-cell or to insulin-sensitive tissues. We have noted that with insulin resistance the fasting plasma glucose is often normal and severe hyperglycaemia occurs after a glucose load. By contrast, in glucokinase-deficient diabetes, which is characterised by reduced insulin secretion, the reverse is the case. Supportive evidence showing that beta-cell dysfunction and insulin resistance may have different effects on fasting and post-prandial glucose concentrations comes from studies of identical twins of NIDDM patients, hemi-pancreatectomised normal subjects, and insulin-resistant Asian subjects. NIDDM is usually preceded by a period of less severe hyperglycemia, referred to as impaired glucose tolerance (IGT). Studies of the IGT phase usually conclude that insulin resistance is the major abnormality and is thus the primary defect in NIDDM. However, the definition of IGT is based on the 2 h plasma glucose after an oral glucose-tolerance test without consideration of the fasting glucose concentrations (provided these concentrations are non-diabetic). Our observations suggest that this definition of IGT may result in the over-representation of insulin-resistant individuals and the under-representation of subjects with beta-cell dysfunction in any cross sectional study of IGT. The belief that the prediabetic state of IGT is dominated by insulin resistance may be a self-fulfilling prophesy because of the excessive emphasis put on the post-prandial rather than the fasting state.

Blood Glucose↗
PubMed1994

Increased glucose effectiveness in normoglycemic but insulin-resistant relatives of patients with non-insulin-dependent diabetes mellitus. A novel compensatory mechanism.

20 normoglycemic first degree relatives of non-insulin-dependent diabetes mellitus (NIDDM) patients were compared with 20 matched subjects without any family history of diabetes using the intravenous glucose tolerance test with minimal model analysis of glucose disappearance and insulin kinetics. Intravenous glucose tolerance index (Kg) was similar in both groups (1.60 +/- 0.14 vs 1.59 +/- 0.18, x 10(-2) min-1, NS). However, insulin sensitivity (Si) was reduced (3.49 +/- 0.43 vs 4.80 +/- 0.61, x 10(-4) min-1 per mU/liter, P = 0.05), whereas glucose effectiveness (Sg) was increased (1.93 +/- 0.14 vs 1.52 +/- 0.16, x 10(-2) min-1, P < 0.05) in the relatives. Despite insulin resistance neither fasting plasma insulin concentration (7.63 +/- 0.48 vs 6.88 +/- 0.45, mU/liter, NS) nor first phase insulin responsiveness (Phi1) (3.56 +/- 0.53 vs 4.13 +/- 0.62, mU/liter min-1 per mg/dl, NS) were increased in the relatives. Phi1 was reduced for the degree of insulin resistance in the relatives so that the Phi1 x Si index was lower in the relatives (11.5 +/- 2.2 vs 16.7 +/- 2.0, x 10(-4) min-2 per mg/dl, P < 0.05). Importantly, glucose effectiveness correlated with Kg and with basal glucose oxidation but not with total glucose transporter 4 (GLUT4) content in a basal muscle biopsy. In conclusion we confirm the presence of insulin resistance in first degree relatives of NIDDM patients. However, insulin secretion was altered and reduced for the degree of insulin resistance in the relatives, whereas glucose effectiveness was increased. We hypothesize that increased glucose effectiveness maintains glucose tolerance within normal limits in these "normoinsulinemic" relatives of NIDDM patients.

Adult↗
PubMed1994

Pronounced blood glucose-lowering effect of the antilipolytic drug acipimox in noninsulin-dependent diabetes mellitus patients during a 3-day intensified treatment period.

Acute administration of the antilipolytic nicotinic acid analog acipimox to patients with noninsulin-dependent diabetes mellitus (NIDDM) is associated with increased peripheral and hepatic insulin sensitivity. However, long term acipimox treatment (250 mg, 3 times/24 h) of NIDDM patients does not improve blood glucose control, possibly due to rebound lipolysis. The current study assessed the influence of intensified acipimox administration (125 mg, 12 times/24 h) on diurnal plasma profiles of glucose, insulin, nonesterified FFA (NEFA), and triglycerides during a 3-day period. Eight NIDDM patients [mean age, 58.9 yr (range, 46-68); mean body mass index, 31.4 kg/m2 (range, 24.9-39.6)] were included in a randomized, double blind, placebo-controlled, cross-over study. Blood samples were collected every second hour during the study. The acipimox and placebo treatments were separated by a 2-week washout period. Acipimox treatment was associated with reduced diurnal mean plasma concentrations of NEFA [0.26 +/- 0.03 (+/- SEM) vs. 0.63 +/- 0.06 mmol/L; P < 0.001], triglycerides (1.74 +/- 0.21 vs. 2.10 +/- 0.18 mmol/L; P < 0.03), glucose (12.7 +/- 1.0 vs. 15.8 +/- 1.2 mmol/L; P < 0.002), and insulin (157 +/- 21 vs. 207 +/- 27 pmol/L; P < 0.05). However, despite the overall reduction in mean NEFA, during acipimox treatment NEFA increased from days 1-3 (0.18 +/- 0.03 vs. 0.34 +/- 0.04 mmol/L; P < 0.001), whereas plasma glucose (13.4 +/- 1.2 vs. 12.3 +/- 0.9 mmol/L; P < 0.03) and plasma insulin (168 +/- 23 vs. 148 +/- 17 pmol/L; P < 0.04) decreased steadily from days 1-3 during active treatment. In conclusion, inhibition of lipolysis using the intensified acipimox treatment regiment was associated with a pronounced blood glucose- and plasma insulin-lowering effect. However, minor rebound effects of lipolysis occurred in some patients despite the presence of allegedly effective acipimox levels. This suggests that caution should be employed concerning long term use of acipimox as a hypoglycemic agent in NIDDM patients.

Blood Glucose↗
PubMed1993

Impact of injection sites for soluble insulin on glycaemic control in type 1 (insulin-dependent) diabetic patients treated with a multiple insulin injection regimen.

The absorption rate of rapid acting (soluble) insulin is slow from the subcutaneous tissue of the thigh compared to intramuscular injection into the thigh and s.c. injection into the abdominal wall. The aim of the study was to evaluate the impact of soluble insulin injected either intramuscularly into the thigh (IMT), s.c. into the abdominal wall (SCA) or s.c. into the thigh (SCT) on glycaemic control in Type 1 (insulin-dependent) diabetic outpatients treated with the basal bolus insulin delivery regimen. Fifty-five, C-peptide negative Type 1 diabetic outpatients were included in a randomised 3-month intervention study. The insulin doses were adjusted frequently by blinded observers based on the patients' self-monitored blood glucose values and reported hypoglycaemic episodes. The serum fructosamine value was within normal limits in three patients in the IMT group, in six patients in the SCA group and in none of the patients in the SCT group following the intervention period (p < 0.01). However, the difference in mean serum fructosamine values did not reach statistical significance (IMT: 1.24 mmol/l (95% confidence interval; 1.17 to 1.31), SCA: 1.25 mmol/l (1.18 to 1.32), SCT: 1.34 mmol/l (1.26 to 1.41), (p = 0.09). Blood glucose excursions were larger in the SCT group than in the SCA and IMT group from post-lunch to pre-dinner measurements and from pre- to post-dinner measurements. A higher number of measured low nocturnal blood glucose values (less than 4 mmol/l) was observed in the SCT group (34 of 85) than in the IMT (14 of 64) and SCA (21 of 81) group (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1993

Decreased tyrosine kinase activity in partially purified insulin receptors from muscle of young, non-obese first degree relatives of patients with type 2 (non-insulin-dependent) diabetes mellitus.

Recently, we demonstrated insulin resistance due to reduced glucose storage in young relatives of Type 2 diabetic patients. To investigate whether this was associated with a defective insulin receptor kinase, we studied ten of these young (27 +/- 1 years old) non-obese glucose tolerant first degree relatives of patients with Type 2 diabetes and eight matched control subjects with no family history of diabetes. Insulin sensitivity was assessed by a hyperinsulinaemic, euglycaemic clamp. Insulin receptors were partially purified from muscle biopsies obtained in the basal and the insulin-stimulated state during the clamp. Insulin binding capacity was decreased by 28% in the relatives (p < 0.05) in the basal biopsy. Tyrosine kinase activity in the receptor preparation was decreased by 50% in both basal and insulin-stimulated biopsies from the relatives. After stimulation with insulin "in vitro", kinase activity was reduced in the relatives in basal (p < 0.005) and insulin-stimulated (p < 0.01) biopsies and also when expressed per insulin binding capacity (p approximately 0.05). Insulin stimulation of non-oxidative glucose metabolism correlated with "in vitro" insulin-stimulated tyrosine kinase activity (r = 0.61, p < 0.01) and also when expressed per binding capacity (r = 0.53, p < 0.025). We suggest that the marked defect in tyrosine kinase activity in partially purified insulin receptors from skeletal muscle is an early event in the development of insulin resistance and contributes to the pathophysiology of Type 2 diabetes.

Adult↗
PubMed1993

Effect of hyperglycemia per se on glucose turnover rates in patients with insulin-dependent diabetes.

The effect of hyperglycemia, per se, on glucose utilization and hepatic glucose production was reevaluated in eight C-peptide-negative insulin-dependent diabetic patients using primed-continuous noncontaminated 3-3H-glucose infusion and labeled glucose infusates. The night before study, euglycemia was maintained by a variable insulin infusion. During the studies, insulin was infused at basal replacement rates determined as the rate required to maintain euglycemia in the morning. After a 2-hour equilibration period, either plasma glucose level was increased to 12 mmol/L for 4 hours using a variable glucose infusion, or no glucose was infused (control day). On the hyperglycemic day, glucose utilization increased 16% (86 +/- 2 to 99 +/- 4 mg.m-2.min-1, P < .02) and glucose production decreased 45% (85 +/- 3 to 47 +/- 4 mg.m-2.min-1, P < .01). On the control day, both glucose utilization and glucose production decreased (84 +/- 3 to 68 +/- 3 and 84 +/- 3 to 65 +/- 3 mg.m-2.min-1, respectively; both P < .01). Therefore, comparing rates at the end of the hyperglycemic and control studies, glucose utilization was increased by 45% and glucose production was decreased by 28% in response to hyperglycemia (both P < .01). Thus hyperglycemia, at basal insulin levels enhanced glucose utilization and suppressed glucose production in insulin-dependent diabetic patients. Quantitatively, the enhancement of glucose utilization was more important than the suppressive effect on glucose production.

Adult↗
PubMed1992

Hyperglycaemia compensates for the defects in insulin-mediated glucose metabolism and in the activation of glycogen synthase in the skeletal muscle of patients with type 2 (non-insulin-dependent) diabetes mellitus.

Insulin resistance and a defective insulin activation of the enzyme glycogen synthase in skeletal muscle during euglycaemia may have important pathophysiological implications in Type 2 (non-insulin-dependent) diabetes mellitus. Hyperglycaemia may serve to compensate for these defects in Type 2 diabetes by increasing glucose disposal through a mass action effect. In the present study, rates of whole-body glucose oxidation and glucose storage were measured during fasting hyperglycaemia and isoglycaemic insulin infusion (40 mU.m-2.min-1, 3 h) in 12 patients with Type 2 diabetes. Eleven control subjects were studied during euglycaemia. Biopsies were taken from the vastus lateralis muscle. Fasting and insulin-stimulated glucose oxidation, glucose storage and muscle glycogen synthase activation were all fully compensated (normalized) during hyperglycaemia in the diabetic patients. The insulin-stimulated increase in muscle glycogen content was the same in the diabetic patients and in the control subjects. Besides hyperglycaemia, the diabetic patients had elevated muscle free glucose and glucose 6-phosphate concentrations. A positive correlation was demonstrated between intracellular free glucose concentration and muscle glycogen synthase fractional velocity insulin activation (0.1 mmol/l glucose 6-phosphate: r = 0.65, p less than 0.02 and 0.0 mmol/l glucose 6-phosphate: r = 0.91, p less than 0.0001). In conclusion, this study indicates an important role for hyperglycaemia and elevated muscle free glucose and glucose 6-phosphate concentrations in compensating (normalizing) intracellular glucose metabolism and skeletal muscle glycogen synthase activation in Type 2 diabetes.

Blood Glucose↗
PubMed1992

A simple method for quantitation of insulin sensitivity and insulin release from an intravenous glucose tolerance test.

Both insulin secretion and insulin sensitivity are important in the development of diabetes but current methods used for their measurements are complex and cannot be used for epidemiological surveys. This study describes a simplified approach for the estimation of first phase insulin release and insulin sensitivity from a standard 40-min intravenous glucose tolerance test (IVGTT), and compares these parameter estimations with the sophisticated minimal model analysis of a frequently sampled 3-h IVGTT and the euglycaemic clamp technique. For the simplified IVGTT, first phase insulin release was measured as the insulin area above basal post glucose load unit-1 incremental change (i.e. peak rise) in plasma glucose over 0-10 min, and insulin sensitivity as a rate of glucose disappearance (Kg) unit-1 insulin increase above basal from 0-40 min post-glucose load in 18 subjects who were studied twice, either basally or in a perturbed pathophysiological state (i.e. pre- and post-ultramarathon race, n = 5; pre- and post-20 h pulsatile hyperinsulinaemia, n = 8; pre- and post-thyrotoxic state, n = 5). A further 12 subjects were compared by IVGTT, and glucose clamp. In addition, seven dogs were studied three times by IVGTT during normal saline infusion and after short-term (1/2 hour) or long-term (72 hour) adrenaline infusions. First phase insulin release and insulin sensitivity estimated from the simplified IVGTT as calculated by the two methods correlated closely (rs = 0.89 and rs = 0.87, respectively), although less precisely in markedly insulin-resistant subjects and the slopes and y intercepts of the linear regression lines were similar in the basal and perturbed states.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1992

Intranasal administration of insulin with phospholipid as absorption enhancer: pharmacokinetics in normal subjects.

The pharmacokinetics of intranasal insulin containing a medium-chain phospholipid (didecanoyl-L-alpha-phosphatidylcholine) as absorption enhancer, was studied in normal volunteers by measuring plasma glucose, insulin, C-peptide, and glucagon. Eleven fasting subjects received 4 U insulin intravenously, 6 U subcutaneously, or three doses intranasally (approximately 0.3 U kg-1, 0.6 U kg-1, 0.8 U kg-1) in random order on five separate days. Intranasal insulin was absorbed in a dose-dependent manner with a mean plasma insulin peak 23 +/- 7 (+/- SE) min after administration. Mean plasma glucose nadir was seen after 44 +/- 6 min, 20 min later than following intravenous injection. Furthermore, intranasal administration of insulin resulted in a faster time-course of absorption than subcutaneous injection, with significantly reduced intersubject variation (p less than 0.001). Bioavailability for the nasal formulation was 8.3% relative to an intravenous bolus injection when plasma insulin was corrected for endogenous insulin production estimated by C-peptide. A dose-dependent suppression of C-peptide and stimulation of glucagon secretion occurred after intranasal administration of insulin. Nasal irritation from spraying was absent or slight.

Absorption↗
PubMed1992

Decreased insulin activation of glycogen synthase in skeletal muscles in young nonobese Caucasian first-degree relatives of patients with non-insulin-dependent diabetes mellitus.

Insulin resistance in non-insulin-dependent diabetes is associated with a defective insulin activation of the enzyme glycogen synthase in skeletal muscles. To investigate whether this may be a primary defect, we studied 20 young (25 +/- 1 yr) Caucasian first-degree relatives (children) of patients with non-insulin-dependent diabetes, and 20 matched controls without a family history of diabetes. Relatives and controls had a normal oral glucose tolerance, and were studied by means of the euglycemic hyperinsulinemic clamp technique, which included performance of indirect calorimetry and muscle biopsies. Insulin-stimulated glucose disposal was decreased in the relatives (9.2 +/- 0.6 vs 11.5 +/- 0.5 mg/kg fat-free mass per (FFM) min, P less than 0.02), and was due to a decreased rate of insulin-stimulated nonoxidative glucose metabolism (5.0 +/- 0.5 vs 7.5 +/- 0.4 mg/kg fat-free mass per min, P less than 0.001). The insulin-stimulated, fractional glycogen synthase activity (0.1/10 mmol liter glucose-6-phosphate) was decreased in the relatives (46.9 +/- 2.3 vs 56.4 +/- 3.2%, P less than 0.01), and there was a significant correlation between insulin-stimulated, fractional glycogen synthase activity and nonoxidative glucose metabolism in relatives (r = 0.76, P less than 0.001) and controls (r = 0.63, P less than 0.01). Furthermore, the insulin-stimulated increase in muscle glycogen content over basal values was lower in the relatives (13 +/- 25 vs 46 +/- 9 mmol/kg dry wt, P = 0.05). We conclude that the defect in insulin activation of muscle glycogen synthase may be a primary, possibly genetically determined, defect that contributes to the development of non-insulin-dependent diabetes.

Adult↗
PubMed1992

Effect of acute hyperglycemia on glucose metabolism in skeletal muscles in IDDM patients.

The effect of acute hyperglycemia on glucose metabolism in skeletal muscles was assessed during replacement insulin infusion in 11 patients with insulin-dependent diabetes mellitus (IDDM). With a primed continuous [3-3H]glucose infusion and indirect calorimetry, glucose metabolism was assessed during a basal period (plasma glucose [PG] 5 mM) and during a hyperglycemic period (4-h i.v. glucose infusion, PG 12.1 mM). Biopsies were taken from the vastus lateralis muscle during both periods. On a control day, glucose metabolism was assessed in 10 patients during a basal period (PG 5.2 mM) and after 4 h with no glucose infusion (PG 4.2 mM). Nonoxidative glucose disposal increased during hyperglycemia (32 +/- 7 vs. 51 +/- 9 mg.m-2.min-1, P less than 0.05), whereas glucose oxidation remained constant. On the control day, nonoxidative glucose disposal decreased from the basal to the second (control) period (33 +/- 7 vs. 22 +/- 6 mg.m-2.min-1, P less than 0.05), and glucose oxidation remained constant. The activity of glycogen synthase in muscle biopsies (fractional velocities [0.1 and 10 mM glucose 6-phosphate (G6P)]) decreased slightly during hyperglycemia (18 +/- 2 vs. 12 +/- 2%, P less than 0.05) and on the control day (26 +/- 4 vs. 20 +/- 3%, P less than 0.05). Hyperglycemia increased the intracellular concentration of free glucose, corrected for estimated extracellular glucose (0.56 +/- 0.11 vs. 1.43 +/- 0.19 mM, P less than 0.01), G6P (0.14 +/- 0.04 vs. 0.23 +/- 0.08 mM, P less than 0.02), and lactate (2.88 +/- 0.33 vs. 4.46 +/- 0.61 mM, P less than 0.05), whereas these substrate concentrations remained constant on the control day.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1992

Insulin resistance in skeletal muscles in patients with NIDDM.

Skeletal muscles in patients with non-insulin-dependent diabetes mellitus (NIDDM) are resistant to insulin; i.e., the effect of insulin on glucose disposal is reduced compared with the effect in control subjects. This defect has been found to be localized to the nonoxidative pathway of glucose disposal; hence, the deposition of glucose, as glycogen, is abnormally low. This defect may be inherited, because it is present in first-degree relatives to NIDDM patients two to three decades before they develop frank diabetes mellitus. The cellular defects responsible for the abnormal insulin action in NIDDM patients is reviewed in this article. The paper focuses mainly on convalent insulin signaling. Insulin is postulated to stimulate glucose storage by initiating a cascade of phosphorylation and dephosphorylation events, which results in dephosphorylation and hence activation of the enzyme glycogen synthase. Glycogen synthase is the key enzyme in regulation of glycogen synthesis in the skeletal muscles of humans. This enzyme is sensitive to insulin, but in NIDDM patients it has been shown to be completely resistant to insulin stimulation when measured at euglycemia. The enzyme seems to be locked in the glucose-6-phosphate (G-6-P)-dependent inactive D-form. This hypothesis is favored by the finding of reduced activity of the glycogen synthase phosphatase and increased activity of the respective kinase cAMP-dependent protein kinase. A reduced glycogen synthase activity has also been found in normoglycemic first-degree relatives of NIDDM patients, indicating that this abnormality precedes development of hyperglycemia in subjects prone to develop NIDDM. Therefore, this defect may be of primary genetic origin. However, it does not appear to be a defect in the enzyme itself, but rather a defect in the covalent activation of the enzyme system. Glycogen synthase is resistant to insulin but may be activated allosterically by G-6-P. This means that the defect in insulin activation can be compensated for by increased intracellular concentrations of G-6-P. In fact, we found that both hyperinsulinemia and hyperglycemia are able to increase the G-6-P level in skeletal muscles. Thus, insulin resistance in the nonoxidative pathway of glucose processing can be overcomed (compensated) by hyperinsulinemia and hyperglycemia. In conclusion, we hypothesize that insulin resistance in skeletal muscles may be a primary genetic defect preceding the diabetic state. The cellular abnormality responsible for that may be a reduced covalent insulin activation of the enzyme glycogen synthase.(ABSTRACT TRUNCATED AT 400 WORDS)

Diabetes Mellitus, Type 2↗
PubMed1991

Prevalence of micro- and macroalbuminuria, arterial hypertension, retinopathy and large vessel disease in European type 2 (non-insulin-dependent) diabetic patients.

The prevalence of micro- and macroalbuminuria was determined in Type 2 (non-insulin-dependent) diabetic patients, less than 76 years of age, attending a diabetic clinic during 1987. All eligible patients (n = 557) were asked to collect a 24-h urine sample for quantitative albumin analysis. Urine collections were obtained in 296 males and 253 females (96%). Normoalbuminuria were defined as urinary albumin excretion less than or equal to 30 mg/24 h (n = 323), microalbuminuria as 31-299 mg/24 h (n = 151), and macroalbuminuria as greater than or equal to 300 mg/24 h (n = 75). The prevalence of macroalbuminuria was significantly higher in males (20%) than in females (6%), while the prevalence of microalbuminuria was almost identical in males (26%) and females (29%). The prevalence of arterial hypertension increased with increased albuminuria, being 48%, 68%, and 85% in patients with normoalbuminuria, microalbuminuria, and macroalbuminuria respectively. Prevalence of proliferative retinopathy rose with increasing albuminuria, being 2%, 5% and 12% in patients with normoalbuminuria, microalbuminuria, and macroalbuminuria respectively. Prevalence of coronary heart disease, based on Minnesota coded electrocardiograms, was more frequent in patients with macroalbuminuria (46%) compared to patients with microalbuminuria (26%) and patients with normoalbuminuria (22%). Foot ulcers were more frequent in micro- and macroalbuminuric patients, being 13% and 25%, respectively, compared to 5% in patients with normoalbuminuria. This cross-sectional study has revealed a high prevalence of microalbuminuria (27%) and macroalbuminuria (14%) in Type 2 diabetic patients. Patients with raised urinary albumin excretion are characterized by obesity, elevated haemoglobin Alc, increased frequency of arterial hypertension, proliferative retinopathy, coronary heart disease and foot ulcers.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1991

Reduced glycogen synthase activity in skeletal muscle from obese patients with and without type 2 (non-insulin-dependent) diabetes mellitus.

In order to evaluate the importance of a defect in insulin mediated non-oxidative glucose metabolism and glycogen synthase activity in skeletal muscles in obese subjects with and without Type 2 (non-insulin-dependent) diabetes mellitus we studied: 10 lean and 10 obese control subjects and 12 obese diabetic patients using the euglycaemic hyperinsulinaemic clamp technique (basal, 20 mU.(m2)-1.min-1, 80 mU.(m2)-1.min-1) in combination with indirect calorimetry. Muscle biopsies were taken from m. vastus lateralis at each insulin level. We found that non-oxidative glucose metabolism could be stimulated by insulin in all three groups (p less than 0.01). The values obtained at the highest insulin levels (around 140 microU/ml) were lower in both obese groups compared to the lean control subjects (118 +/- 21, 185 +/- 31, 249 +/- 14 mg.(m2)-1.min-1 (p less than 0.01]. Insulin stimulation of the glycogen synthase activity at a glucose-6-phosphate concentration of 0.1 mmol/l was absent in both obese groups, while activities increased significantly in the lean control subjects (19.6 +/- 4.2% to 45.6 +/- 6.8%, p less than 0.01). Glycogen synthase activities at the highest insulin concentrations only differed significantly between lean control subjects and obese diabetic patients (45 +/- 7% and 31 +/- 5%, p less than 0.05). We conclude that insulin resistance in peripheral tissues in obese subjects with and without Type 2 diabetes may be partly explained by a reduced insulin mediated non-oxidative glucose metabolism and that this abnormality might be due to an absent insulin stimulation of glycogen synthase in skeletal muscles. This enzyme defect is correlated to obesity itself.

Allosteric Regulation↗
PubMed1991

Effect of insulin on renal sodium handling in hyperinsulinaemic type 2 (non-insulin-dependent) diabetic patients with peripheral insulin resistance.

The sodium retaining effect of insulin was studied in ten Type 2 (non-insulin-dependent) diabetic patients (mean age 56 (43-73) years, mean body mass index 29.5 (24.2-33.7) kg/m2) and eight age-matched control subjects (mean age 57 (43-68) years, mean body mass index 23.4 (20.8-26.6) kg/m2). The renal clearances of 99mTc-DTPA, lithium, sodium and potassium were measured over a basal period of 90 min. Then insulin was infused at a rate of 40 mU.min-1.m-2. After an equilibration period of 90 min, the clearance measurements were repeated during a new 90 min period. Blood glucose was clamped at the basal level (diabetic patients: 9.9 +/- 3.5, control subjects: 5.3 +/- 0.5 mmol/l) by a variable glucose infusion. Basal plasma insulin concentration was elevated in the diabetic patients (0.12 +/- 0.05 vs 0.05 +/- 0.02 pmol/ml, p less than 0.01). Insulin infusion resulted in comparable absolute increments in plasma insulin concentrations in the diabetic group and in the control group (0.44 +/- 0.13 vs 0.36 +/- 0.07 pmol/ml, NS). The metabolic clearance rate of glucose during the last 30 min of insulin infusion was lower in the diabetic patients (155 +/- 62 vs 320 +/- 69 ml.min-1.m-2, p less than 0.01), reflecting peripheral insulin resistance. The decline in sodium clearance during insulin infusion was similar in diabetic subjects (1.8 +/- 1.1 vs 0.7 +/- 0.4 ml.min-1.1.73 m-2, p less than 0.01) and in control subjects (1.7 +/- 0.3 vs 0.8 +/- 0.3 ml.min-1.1.73 m-2, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1991

Absorption of NPH (isophane) insulin in resting diabetic patients: evidence for subcutaneous injection in the thigh as the preferred site.

The absorption kinetics of NPH (isophane) insulin injected subcutaneously into the abdominal wall and subcutaneously (SC) and intramuscularly (IM) into the thigh was studied in 11 Type 1 diabetic patients. The thickness of the subcutaneous adipose tissue layer was measured by ultrasound. NPH (isophane) insulin injected IM into the thigh was absorbed faster than NPH insulin injected SC into the thigh (T50%, IM 8.0 +/- 0.6 h and SC 10.3 +/- 0.7 h, p less than 0.05). No difference in T50% values was found for injection into the abdominal wall (9.7 +/- 1.2h) compared with the thigh. The mean absorption rate from 1.5 to 13.5 h after injection was higher after injection IM into the thigh (6.4 +/- 0.3% of initial dose injected absorbed per h) than after SC injection into the thigh (5.2 +/- 0.3% h-1) and SC into the abdominal wall (5.1 +/- 0.3% h-1) (p less than 0.01). The most constant absorption rate was obtained after SC injection into the thigh (within-study day CV of the mean absorption rate 19.9 +/- 3.2% vs 34.4 +/- 3.2% after IM injection into the thigh and 27.1 +/- 4.9% after SC injection into the abdominal wall (p less than 0.02]. The study provides further evidence that the subcutaneous tissue of the thigh is the preferred injection site for NPH insulin.

Absorption↗