Torbjörn Lindström

Fast food based hyper-alimentation can induce rapid and profound elevation of serum alanine aminotransferase in healthy subjects

Objective: To study the effect of fast-food-based hyper-alimentation on liver enzymes and hepatic triglyceride content (HTGC). Design: Prospective interventional study with parallel control group. Setting: University Hospital of Linköping, Sweden. Participants: 12 healthy men and six healthy women with a mean (SD) age of 26 (6.6) years and a matched control group. Intervention: Subjects in the intervention group aimed for a body weight increase of 5–15% by eating at least two fast-food-based meals a day with the goal to double the regular caloric intake in combination with adoption of a sedentary lifestyle for 4 weeks. Main outcome measures: Weekly changes of serum aminotransferases and HTGC measured by proton nuclear magnetic resonance spectroscopy at baseline and after the intervention. Results: Subjects in the intervention group increased from 67.6 (9.1) kg to 74.0 (11) kg in weight (p<0.001). Serum ALT increased from 22.1 (11.4) U/l at study start to an individual mean maximum level of 97 (103) U/l (range 19.4–447 U/l). Eleven of the 18 subjects persistently showed ALT above reference limits (women >19 U/l, men >30 U/l) during the intervention. Sugar (mono- and disaccharides) intake during week 3 correlated with the maximal ALT/baseline ALT ratio (r = 0.62, p = 0.006). HTGC increased from 1.1 (1.9)% to 2.8 (4.8)%, although this was not related to the increase in ALT levels. ALT levels were unchanged in controls. Conclusion: Hyper-alimentation per se can induce profound ALT elevations in less than 4 weeks. Our study clearly shows that in the evaluation of subjects with elevated ALT the medical history should include not only questions about alcohol intake but also explore whether recent excessive food intake has occurred.

A comparison a amitriptyline and maprotiline in the treatment of painful polyneuropathy in diabetics and nondiabetics.

OBJECTIVE To compare amitriptyline and maprotiline in the treatment of painful polyneuropathy in diabetics and nondiabetics. DESIGN A double-blind, crossover trial of treatment with amitriptyline, maprotiline, and placebo. Treatment was given in randomized order for periods of 4 weeks. Each period was separated by a 1-week washout. The final dose was 75 mg/day for both amitriptyline and maprotiline. PATIENTS Thirty-seven patients with diabetic and nondiabetic painful polyneuropathy. OUTCOME MEASURES The treatment effects were assessed by daily ratings of pain intensity on a 10-step verbal scale (0 = no pain and 10 = worst thinkable pain) and at the end of each treatment period by a global rating of the analgesic effect on a 5-step verbal scale (pain relief scale). For the assessment of depression, the Comprehensive Psychopathological Rating Scale (CPRS) was used. RESULTS Using the global assessment of pain relief at the end of each treatment period, 22 of 33 patients reported reduced pain on amitriptyline treatment compared with 14 of 33 patients on maprotiline treatment and 8 patients on placebo treatment (p < .0001 and p < .05 for amitriptyline and maprotiline, respectively, against placebo). Amitriptyline was slightly better than maprotiline (p < .05) [tested by repeated measures analysis of variance (ANOVA)]. The order in which treatments occurred and the diagnosis of diabetes or nondiabetes did not have any significant effect on the global rating of pain relief. The mean values of the daily ratings of pain intensity showed that pain was more severe in the evenings than in the mornings and that diabetic patients reported worse pain than nondiabetics at baseline. The mean values of pain reduction as assessed with the 10-step verbal scale during the 4th week of treatment showed that amitriptyline and maprotiline were significantly better than placebo in relieving the pain (p < .0001 and p < .01, respectively, post hoc test according to Scheffé). However, there was no significant difference between the pain reduction of amitriptyline compared with maprotiline when assessing pain reduction with the 10-step verbal scale during the 4th treatment week. Nor was there a significant difference between diabetics and nondiabetics with regard to the effect of the drugs. The clinical effect was not significantly correlated to plasma concentration of either amitriptyline and its active metabolite nortriptyline or maprotiline in the global or daily assessments. The effect of treatment was not correlated to any particular pain quality nor to the intensity of pain. Depression was noted in three patients who completed the medication trial, but the effect of treatment of pain and depression did not clearly correlate. The adverse side effects of amitriptyline and maprotiline were common, and in 5 patients the medication had to be discontinued because of severe side effects. CONCLUSION From the present results and the literature, it is concluded that tricyclic antidepressants with a pharmacologic profile similar to amitriptyline are the most effective drugs in the treatment of polyneuropathy pain in both diabetic and nondiabetic patients.

Hypoglycaemia and Cardiac Arrhythmias in Patients with Type 2 Diabetes Mellitus

Improved blood glucose control by insulin treatment in patients with Type 2 (non‐insulin dependent) diabetes mellitus increases the risk for hypoglycaemic episodes. Our objective was to investigate if hypoglycaemia causes electrocardiographic changes and cardiac arrhythmias in patients with Type 2 diabetes. Six insulin‐treated patients with Type 2 diabetes and no known cardiac disease took part in the study. Hypoglycaemia was induced by insulin infusion aiming at a plasma glucose ≥ 2.0 mmol I−1 or hypoglycaemic symptoms. All patients experienced hypoglycaemic symptoms. The median lowest arterial plasma glucose was 2.0 mmol I−1. Arterial plasma adrenaline concentration increased from 0.4 ± 0.1 (mean ± SE) to 6.9 ±0.3 nmol I−1 (p < 0.001) while serum potassium was lowered from 4.1 ± 0.3 mmol I−1 to 3.5 ± 0.2 mmol I−1 (p < 0.001). The heart rate increased significantly during hypoglycaemia except in one patient who developed hypoglycaemic symptoms and a severe bradyarrhythmia at a plasma glucose of 4.4 mmol I−1. One patient developed frequent ventricular ectopic beats during hypoglycaemia while four patients showed no arrhythmia. ST‐depression in ECG leads V2 and V6 was observed during hypoglycaemia in five patients (p < 0.05) and four patients developed flattening of the T‐wave.

Serum leptin concentrations in a normal population and in GH deficiency: Negative correlation with testosterone in men and effects of GH treatment

To study relationships between leptin and factors regulating body composition as well as metabolic risk factors. Furthermore, to study the effects of GH on leptin.

Insulin-induced GLUT4 translocation to the plasma membrane is blunted in large compared with small primary fat cells isolated from the same individual

Aims/hypothesisSeveral studies have suggested that large fat cells are less responsive to insulin than small fat cells. However, in these studies, large fat cells from obese individuals were compared with smaller fat cells from leaner participants, in effect making it impossible to draw conclusions about whether there is a causal relationship between fat cell size and insulin sensitivity. We hypothesised that small fat cells might be more insulin-responsive than large adipocytes when obtained from the same individual.Materials and methodsWe developed a method of sorting isolated primary human fat cells by using nylon filters of two different pore sizes. The cells were stained to visualise DNA, which allowed discrimination from artefacts such as lipid droplets. The sorted cells were left to recover overnight, since we had previously demonstrated that this is necessary for correct assessment of insulin response.ResultsWe found similar amounts of the insulin receptor (IR), IRS-1 and GLUT4 when we compared small and large adipocytes from the same volunteer by immunoblotting experiments using the same total cell volume from both cell populations. Activation of IR, IRS-1 and Akt1 (also known as protein kinase B) by insulin was similar in the two cell populations. However, immunofluorescence confocal microscopy of plasma membrane sheets did not reveal any increase in the amount of GLUT4 in the plasma membrane following insulin stimulation in the large fat cells, whereas we saw a twofold increase in the amount of GLUT4 in the small fat cells.Conclusions/interpretationOur results support a causal relationship between the accumulation of large fat cells in obese individuals and reduced insulin responsiveness.

A randomized, double‐blind, crossover study comparing two‐ and four‐dose hydrocortisone regimen with regard to quality of life, cortisol and ACTH profiles in patients with primary adrenal insufficiency

Current guidelines on how to divide the daily cortisol substitution dose in patients with primary adrenal insufficiency (PAI) are controversial and mainly based on empirical data.

Elevated circulating adiponectin in type 1 diabetes is associated with long diabetes duration

Objective  To study circulating adiponectin concentrations in relation to diabetes duration and endogenous insulin secretion in patients with type 1 diabetes.

Two weeks of overfeeding with candy, but not peanuts, increases insulin levels and body weight

Abstract Objective: To study the effects of snacking based on fast acting carbohydrates (candy) or fat and protein (peanuts) in a prospective randomized, parallel intervention study. Methods: Basal metabolic rate (BMR) and cardiovascular risk factors were measured before and after hyper-alimentation by addition of 20kcal/kg (84kJ/kg) body weight of either candy or roasted peanuts, to the regular caloric intake, for two weeks in healthy subjects. Eleven men and 14 women completed the randomized study. Results: Energy-intake increased similarly in the groups (candy: +46.1±35%, peanuts: +46.8±28% p=0.96). Body-weight (candy: from 67.3±7.6kg to 68.1±7.3kg, p=0.01, nuts: from 68.7±6.1kg to 69.0±5.7kg p=0.3) and waist circumference increased significantly only in the candy group. At the end of the study LDL cholesterol (candy: 2.6±0.4mmol/l peanuts: 2.1±0.4mmol/l, p=0.005) and ApoB/ApoA-1-ratio (candy: 0.68±0.16 peanuts 0.53±0.11, p=0.01) were higher in the candy group than in the peanut group. On the other hand, BMR increased only in the peanut group (candy: from 6.657±1.1MJ/24h to 6.762±1.1MJ/24h, p=0.3 nuts: from 6.896±0.98MJ/24h to 7.256±1.1MJ/24h, p=0.02). Conclusion: Two weeks of snacking based on peanuts does not cause the same negative metabolic effects as an isocaloric diet in which the snacking is based on short acting carbohydrates in the form of candy in non-obese healthy subjects.

Carotid intima-media thickness and apolipoprotein B/apolipoprotein A-I ratio in middle-aged patients with Type 2 diabetes.

Aims  To explore the association between carotid intima‐media thickness (IMT) and the apolipoprotein B (apoB)/apolipoprotein A‐I (apoA‐I) ratio compared with conventional lipids in middle‐aged patients with Type 2 diabetes.

Long-Term Improvement of Glycemic Control by Insulin Treatment in NIDDM Patients With Secondary Failure

OBJECTIVE To evaluate the long-term efficacy of insulin treatment of patients with non-insulin-dependent diabetes mellitus (NIDDM) and secondary failure to oral hypoglycemic agents. RESEARCH DESIGN AND METHODS Twenty one NIDDM patients with secondary failure were studied while they were still on oral agents. Then they were switched to insulin treatment, and after a median of 27 months, a long-term evaluation was conducted. RESULTS At the long-term evaluation, metabolic control was still markedly improved by insulin treatment, with reduction of HbA1c from 8.8 ± 0.2 (mean ± SE) to 6.9 ± 0.3% (P < 0.0001), lowering of very-low-density lipoprotein (VLDL) cholesterol concentration from 0.97 ± 0.3 to 0.69 ± 0.1 mM (P < 0.03), and lowering of total triglycerides from 2.8 ± 0.6 to 1.8 ± 0.3 mM (P < 0.005), mainly due to reduction of VLDL triglycerides. Body weight increased during the first year, but not thereafter (71.3 ± 2.5 kg during oral treatment, 78.9 ± 2.9 and 79.8 ± 3.2 kg after 12 and 36 months of insulin treatment, respectively). Blood pressure did not change. Fasting and postprandial insulin concentrations increased, and C-peptide concentrations were lowered. CONCLUSIONS Improvements of glycemic control and lipoprotein concentrations in patients with NIDDM and secondary failure persist also after insulin treatment for 2–3 years in spite of weight gain and hyperinsulinemia.