Rolf Gunnarsson

Some Characteristics of Steroid Diabetes: A Study in Renal-Transplant Recipients Receiving High-Dose Corticosteroid Therapy

Risk factors and course of steroid diabetes were investigated in 145 renal-transplant recipients who were given a high-dose steroid regimen. Persistent steroid diabetes developed in 25% of the patients and transient diabetes in another 22%. When antidiabetic therapy was required, insulin had to be given in 50%. The incidence of steroid diabetes correlated with steroid dose, age, body weight, and diabetes heredity but not with abnormal glucose tolerance or with another complication of steroid therapy, posterior-pole lenticular cataract. There was no association with HLA-A and B antigens. Thus, steroid diabetes is a frequent complication of high-dose corticosteroid therapy and is similar to type II diabetes. However, it often requires insulin therapy.

Increased peripheral insulin sensitivity and muscle mitochondrial enzymes but unchanged blood glucose control in type I diabetics after physical training

Nine male, insulin-dependent diabetic patients participated in a 16-wk training program consisting of 1 h of jogging, running, ball games, and gymnastics, performed 2-3 times/wk. The training resulted in an 8% increase of maximal oxygen uptake (P < 0.01). Insulin sensitivity as determined by the insulin clamp technique increased 20% (P < 0.05). Glycosylated hemoglobin showed no change (10.4 ± 0.7% versus 11.3 ± 0.5%), 24-h urinary glucose excretion was not reduced, and home-monitored urine tests were unchanged. The frequency of hypoglycemie attacks did not change during the training period and body weight remained constant. There was a 14% fall in plasma cholesterol (P < 0.01) and a rise in the proportion of HDL-cholesterol from 24 ± 2% to 30 ± 3% (P < 0.01). Thigh muscle oxidative capacity increased, as indicated by a 24% increase in succinate dehydrogenase activity (P < 0.05). The number of capillaries/muscle fiber increased 15% (P < 0.01). However, as the mean muscle fiber cross-sectional area increased to a similar extent (11%, P < 0.05), capillary density (cap × mm−2) was unchanged. In conclusion, this study demonstrates that physical training in insulin-dependent diabetics results in increased peripheral insulin sensitivity, a rise in muscle mitochondrial enzyme activities, decreased total plasma cholesterol levels, and unchanged blood glucose control. The findings suggest that in the absence of efforts to alter dietary regulation and insulin administration, physical training consisting of 2-3 weekly bouts of moderate exercise may not of itself improve blood glucose control in type I diabetes.

EFFECTS OF COMBINED PANCREATIC AND RENAL TRANSPLANTATION ON DIABETIC NEUROPATHY: A TWO-YEAR FOLLOW-UP STUDY

To investigate whether diabetic neuropathy can be reversed after pancreatic transplantation 13 diabetic patients were examined by means of conventional electroneurography and tests on autonomic function before and 6, 12, and 24 months after combined renal and pancreatic transplantation. 15 diabetic patients receiving a kidney graft only and 15 non-diabetic kidney graft recipients served as controls. Before transplantation neuropathy was most advanced in the two diabetic groups. Both diabetic groups showed a similar slight but significant improvement of nerve conduction after transplantation. In the non-diabetic group nerve conduction became essentially normal. No group showed improvement in autonomic dysfunction. The improvement in nerve conduction after combined kidney and pancreas transplantation was most probably due to the elimination of uraemia. Furthermore, 2 years of normoglycaemia did not reverse the diabetic neuropathy to an important extent at this late stage of the disease.

Residual insulin production, glycaemic control and prevalence of microvascular lesions and polyneuropathy in long-term Type 1 (insulin-dependent) diabetes mellitus

SummaryThe aim of the present study was to evaluate the role of residual insulin production in long-term Type 1 (insulin-dependent) diabetes mellitus. Ninety-seven patients with a disease duration of 9–16 years and onset before the age of 30 years were studied. C-peptide excretion in 24-h urine samples was measured as an indicator of residual insulin production. Thirty-five patients (36%) excreted C-peptide (>-0.2 nmol); as many as possible of them were carefully matched with a non-excretor patient with regard to age at onset of diabetes and disease duration. Twenty-nine pairs were obtained, and 22 of them agreed to participate in further investigations of glycaemic control and microangiopathic lesions. The patients who excreted C-peptide had significantly lower HbA1c than the non-excretor group, 6.9±0.3% vs 7.9±0.3%, (p<0.025). Moderate-to-advanced background retinopathy was found in 2 patients in the excretor group and in 7 patients in the nonexcretor group. Microalbuminuria [ratio of albumin: creatinine (mg/l:mmol/l) >-5] was found in 1 and in 5 patients, respectively, while proteinuria [ratio of protein: creatinine (mg/l: mmol/l× 10) >-136] was found in 0 and in 4 patients, respectively. Microalbuminuria and/or proteinuria was found in 7 of the non-excretor group as compared to 1 in the excretor group (p=0.046). When all the variables were taken into account, microalbuminuria and/or proteinuria and/or moderate-to-advanced background retinopathy was found in 3 of the excretor group compared to 11 of the non-excretor group (p=0.022). Reduced sensory and motor nerve conduction velocities were common findings and occurred with the same frequency in the two groups. The data suggest that residual insulin production in long-term Type 1 diabetes is associated with a more satisfactory glycaemic control and a lower prevalence of early microangiopathic eye and kidney lesions.

SUCCESSFUL OUTCOME OF SEGMENTAL HUMAN PANCREATIC TRANSPLANTATION WITH ENTERIC EXOCRINE DIVERSION AFTER MODIFICATIONS IN TECHNIQUE

Segmental pancreatic transplantation is now the most widely favoured form of pancreatic transplantation, but the major difficulty with this procedure is the handling of the exocrine secretion. The use of a pancreaticoenteric anastomosis for exocrine diversion has been re-evaluated and several ancillary measures to reduce the risk of fistula and bacterial contamination have been applied. In three consecutive patients there have been no complications related to the exocrine pancreas. The pancreatic and renal grafts of these patients are functioning well 7, 3, and 2 months, respectively, after transplantation.

Long-term physical training in female Type 1 (insulin-dependent) diabetic patients: absence of significant effect on glycaemic control and lipoprotein levels

SummaryNo objective evidence has been presented to support the beneficial effect of physical training on glycaemic control in Type 1 (insulin-dependent) diabetic patients trained two to three times a week for several months. In the present study we examined the possibility that a daily exercise programme would be more suitable for improving glycaemic control. Thirteen patients completed a 5-month study; 6 were randomized to exercise training (20 min daily bicycle exercise) and 7 served as non-exercising controls. The training resulted in an 8% increase in maximal oxygen uptake (p < 0.05). No change in glycaemic control occurred during the study period in either group. In addition, serum lipid and lipoprotein levels were followed. Total cholesterol decreased during the study period irrespective of training. No effect was noted on the levels of LDL, VLDL, HDL and HDL2 cholesterol. A significant training effect was obtained in the HDL3 subfraction (−10%,p < 0.05). Total triglycerides were unchanged, but a decrease in the level of LDL triglycerides was observed with training (−12%,p < 0.01). It is concluded that, in female Type 1 diabetic patients, daily physical training for several months does not improve glycaemic control and results only in minor changes in serum lipoprotein profiles.

Effects of pancreas transplantation on metabolic and hormonal profiles in IDDM patients.

The diurnal patterns of relevant metabolites and hormones in five pancreas-kidney-transplanted patients (aged 36 ± 2 yr, mean ± SD) with insulindependent diabetes mellitus (IDDM) were compared with those in five kidney-transplanted nondiabetic patients (aged 28 ± 2 yr). The groups were matched for body mass and current dose and type of immunosuppressive treatment. The serum creatinine levels did not differ between the two study groups, but the serum urea level in the nondiabetic patients was slightly but significantly higher than in the diabetic patients. In the pancreas-kidney-transplanted group the investigation was performed 8–47 mo posttransplantation; in the kidney-transplanted nondiabetic patients, 12–18 mo posttransplantation. The mean 24-h levels and rhythms of blood glucose, free fatty acid, 3-hydroxybutyrate, and alanine did not differ between the groups. The mean 24-h levels of blood lactate and glycerol were moderately but significantly higher in the pancreas-kidneytransplanted diabetic patients. At fasting, the level of serum immunoreactive insulin was more than twice as high in the pancreas-kidney-transplanted patients, whereas the plasma C-peptide levels did not differ significantly between the two groups. The mealinduced increases in serum insulin as well as in the plasma C-peptide levels were more marked in the pancreas-kidney-transplanted patients. The findings suggest that the hyperinsulinemia in these patients was due to both the systemic delivery of insulin and an increase in insulin resistance, the latter being particularly apparent in the postprandial phase. In the pancreas-kidney-transplanted patients, elevated plasma glucagon levels were also observed, whereas the mean 24-h level and number of peaks of growth hormone did not differ significantly between the two study groups.

Splanchnic and Renal Exchange of Infused Fructose in Insulin-deficient Type 1 Diabetic Patients and Healthy Controls

Fructose raises blood glucose and lactate levels in normal as well as diabetic man, but the tissue origin (liver and/or kidney) of these responses and the role of insulin in determining the end products of fructose metabolism have not been fully established. Splanchnic and renal substrate exchange was therefore examined during intravenous infusion of fructose or saline in six insulin-deficient type I diabetics who fasted overnight and in five healthy controls. Fructose infusion resulted in similar arterial concentrations and regional uptake of fructose in the two groups. Splanchnic glucose output increased threefold in the diabetics but remained unchanged in controls in response to fructose infusion, and the arterial glucose concentration rose more in diabetics (+5.5 mmol/liter) than in controls (+0.5 mmol/liter). Splanchnic uptake of both lactate and pyruvate increased twofold in response to fructose infusion in the diabetics. In contrast, a consistent splanchnic release of both lactate and pyruvate was seen during fructose infusion in controls. In diabetics fructose-induced hyperglycemia was associated with no net renal glucose exchange, while there was a significant renal glucose production during fructose infusion in the controls. In both groups fructose infusion resulted in renal output of lactate and pyruvate. In the diabetics this release corresponded to the augmented uptake by splanchnic tissues. In two diabetic patients given insulin infusion, all responses to fructose infusion were normalized. Fructose infusion in diabetics did not influence either splanchnic ketone body production or its relationship to splanchnic FFA inflow. We conclude that in insulin-deficient, mildly ketotic type I diabetes, (a) both the liver, by virtue of lactate, pyruvate, and fructose-derived gluconeogenesis, and the kidneys , by virtue of fructose-derived lactate and pyruvate production, contribute to fructose-induced hyperglycemia; (b) outcome of hepatic fructose metabolism; and (c) fructose does not exert an antiketogenic effect. These data suggest that while total fructose metabolism is not altered in diabetics, intermediary hepatic fructose metabolism is dependent on the presence of insulin.

Influence of Physical Training on Formation of Muscle Capillaries in Type I Diabetes

The effects of physical training on skeletal muscle morphology and enzyme activities were compared in 10 male, type I diabetic subjects and 10 healthy, male, control subjects. The training program consisted of running for 45 min, three times per week for 8 wk. Muscle biopsies were obtained before and after the training period from the lateral portion of the gastrocnemius muscle. Pretraining maximal oxygen uptake was similar in the two groups (diabetic subjects 42 ± 1 versus control subjects 43 ± 2 ml × kg−1 × min−1), and the training resulted in an identical increase (+ 13%, P < 0.01). Muscle capillarization (number of capillaries per muscle fiber) increased on the average in the control group (+ 14 ± 4%, P < 0.01), but was unchanged in the diabetic group (0 ± 4%). Capillary density, expressed as number of capillaries per unit muscle cross sectional area, also increased on the average in controls (8 ± 4%, P < 0.05) but failed to do so in the diabetic patients (–8 ± 6%, NS). The activities of the mitochondrial enzymes citrate synthase (+ 26–27%, P < 0.01–0.05) and succinate dehydrogenase (+ 24–25%, P < 0.05) increased significantly and similarly in the two groups, whereas training did not result in significant changes in the activities of the glycolytic enzymes 6-phosphofructokinase and glyceraldehyde-phosphate dehydrogenase. Glycemie control in the diabetic group did not improve with the training, as evaluated from hemoglobin A1 and home-monitored blood glucose. The findings suggest that, compared with controls, the ability to form new skeletal muscle capillaries in response to physical training may be deficient in patients with type I diabetes mellitus of long standing, while the increase in mitochondrial enzyme activities is normal. A deficient formation of new capillaries may be an expression of the microangiopathy of this disorder.

Glucose and Insulin Responses in Relation to Insulin Dose and Caloric Intake 12 h After Acute Physical Exercise in Men With IDDM

Acute exercise in insulin-dependent diabetic patients may perturb glycemic control, and adjustments of insulin and diet might be required to avoid postexercise hypoglycemia. The aim of this study was to assess the role of alterations in insulin dose or caloric intake on blood glucose and free-insulin levels during 12 h after an evening bout of exercise. Nine insulin-dependent diabetic men (28–42 yr of age) receiving two daily injections with a combination of intermediate-acting and soluble insulin participated in the study. Patients were randomly assigned to four treatment protocols: A, 50% reduction in intermediate-acting insulin dose; B, 50% reduction in soluble insulin dose; C, extra caloric intake (1700 kj) 1 h after exercise; and D, no change. Exercise consisted of 45 min of cycling at 60% of maximal oxygen uptake at each occasion. Glucose and insulin responses were similar for the four protocols. There was a significant (P < .001) time effect found regardless of treatment, with lowest blood glucose values 75 min after exercise. Hypoglycemia occurred in six of the nine patients at some time during the study, with half of the occurrences on the control night (protocol D). Consistent individual plasma insulin and glucose patterns were observed independent of protocol used. In some patients, hypoglycemia was evident after reductions in insulin dose, and in others it was evident on the night increases in caloric intake were to occur; thus, none of the interventions were totally adequate in preventing exercise-induced hypoglycemia. In conclusion, general recommendations on how to adjust insulin or diet before exercise are difficult to give. Individualized recommendations for treatment modification appear most appropriate.