Ulf Adamson

Permanent neuropsychological impairment after recurrent episodes of severe hypoglycaemia in man

SummarySeventeen Type 1 (insulin-dependent) diabetic patients with a history of recurrent and severe hypoglycaemia and Type 1 diabetic patients with no severe hypoglycaemia were compared as regarded performances in tests of neuropsychological functioning. To test the hypothesis that recurrent severe hypoglycaemia gives rise to permanent cognitive impairment, the study group was selected among those patients who had met with repeated attacks over the last three years or more as identified by a questionnaire among almost 600 insulin-treated diabetic patients. The comparison group without known severe reactions were comparable to the study group with respect to type of diabetes, sex, age, age at onset, duration of diabetes, socio-economic parameters, and prevalence of neuropathy and retinopathy. The results indicate that Type 1 diabetic patients with recurrent severe hypoglycaemia scored lower than those without severe hypoglycaemia in tests of motor ability, short-term and associative memory and visuospatial tasks assessing ability in general problem-solving. Type 1 diabetic patients with severe hypoglycaemia also displayed a higher frequency of perspective reversals suggesting frontal-lobe involvement. These data can be interpreted in two ways. One interpretation implies that the cognitive impairment of Type 1 diabetic patients with severe hypoglycaemia reflects a selection factor, the other that recurrent episodes of severe hypoglycaemia result in permanent cognitive impairment.

Increased QT dispersion during hypoglycaemia in patients with type 2 diabetes mellitus

Abstract. Landstedt‐Hallin L, Englund A, Adamson U, Lins P‐E (Karolinska Institute, Danderyd Hospital, Danderyd; and Uppsala University Hospital, Uppsala, Sweden). Increased QT dispersion during hypoglycaemia in patients with type 2 diabetes mellitus. J Intern Med 1999; 246: 299–307.

Arterial, arterialized venous, venous and capillary blood glucose measurements in normal man during hyperinsulinaemic euglycaemia and hypoglycaemia

SummaryThe purpose of this study was to evaluate the effectiveness of the warm-air box method on the arterialization of venous blood during euglycaemia and hypoglycaemia. Six healthy male volunteers were studied using an i.v. infusion of insulin (144 mU·kg−1·h−1). Arterial blood glucose was clamped at the baseline level for the first 30 min and subsequently reduced to 3.2 and to 2.5 mmol/l for 20 min. At each stage, including prior to insulin infusion, arterial, arterialized venous (heating the hand in a warm-air box set to 55–60°C), venous and capillary blood samples were taken simultaneously for analyses of blood glucose and oxygen saturation (not for capillary blood). The oxygen saturations in arterialized blood were approximately 3% below the arterial values. The arterial-arterialized difference of blood glucose was about 0.1 mmol/l (the 95% confidence interval: from −0.19 to 0.41 mmol/l), which tended to correlate with the difference in oxygen saturations between the arterial and arterialized blood samples (r=0.25, p=0.08). During the test the forearm venous blood oxygen saturation increased by 9% and the arteriovenous difference in blood glucose ranged from 0.2 to 0.5 mmol/l which correlated significantly with the difference in oxygen saturations (r=0.48, p<0.001). Capillary glucose was similar to the arterialized value. Rectal temperature was stable during the experiment. We conclude that the heated hand technique using the warm-air box sufficiently arterializes venous blood so that the glucose measurement in the arterialized blood provides a reasonable estimate of the arterial value and that the venous blood from the contralateral forearm is also markedly arterialized, probably reflecting a vasodilator effect of heating.

Fear of hypoglycaemia in adults with Type 1 diabetes

Diabet. Med. 27, 1151–1158 (2010)

Comparison of Bedtime NPH or Preprandial Regular Insulin Combined With Glibenclamide in Secondary Sulfonylurea Failure

OBJECTIVE To compare the effect of bedtime NPH insulin or preprandial regular insulin combined with glibenclamide on metabolic control in non-insulin-dependent diabetes mellitus (NIDDM) patients with secondary failure to sulfonylurea therapy. RESEARCH DESIGN AND METHODS Eighty NIDDM patients were randomized to treatment with either three preprandial doses of regular insulin (daytime group D) or a bedtime dose of NPH insulin (nocturnal insulinization, group N), both regimens being combined with 10.5 mg of glibenclamide. Metabolic profiles were obtained at 0, 6, 16 weeks. RESULTS Glycemic control had improved significantly in both groups after 4 months. Fasting blood glucose was significantly lower compared with baseline in both groups. The mean change ± SD in group D was −2.8 ± 3.5 mmol/l and in group N −6.4 ± 3.0 mmol/L, the reduction being more pronounced in group N compared with group D (P < 0.0001). HbA1c was lowered similarly, from 9.2 ± 1.4 to 7.1 ± 1.2% in group D (P < 0.0001) and from 9.1 to 1.1 to 7.5 ± 1.5% in group N (P < 0.0001). The total daily insulin doses were similar, 29 ± 11 U in group D and 26 ± 9 U in group N, and the circulating insulin levels during daytime were higher in group D than in group N. Total serum cholesterol and triglycerides were similarly and significantly lowered compared with baseline in both groups. Weight gain was more pronounced in group D (3.4 ± 0.3 kg) than in group N (1.9 ± 1.9 kg; D vs. N, P < 0.002), and the change was inversely correlated with initial eight but not with the improvement in HbA1c. CONCLUSIONS The two insulin regimens exert similar effect on glucose metabolism and serum lipids in NIDDM patients on combination therapy. Weight gain is more pronounced in patients given insulin during the daytime when preprandial doses of short-acting insulin are used.

A cognitive behavior therapy-based intervention among poorly controlled adult type 1 diabetes patients: a randomized controlled trial

OBJECTIVE To examine the impact of a Cognitive Behavior Therapy (CBT)-based intervention on HbA(1c), self-care behaviors and psychosocial factors among poorly controlled adult type 1 diabetes patients. METHODS Ninety-four type 1 diabetes patients were randomly assigned to either an intervention group or a control group. The intervention was based on CBT and was mainly delivered in group format, but individual sessions were also included. All subjects were provided with a continuous glucose monitoring system (CGMS) during two 3-day periods. HbA(1c), self-care behaviors and psychosocial factors were measured up to 48 weeks. RESULTS Significant differences were observed with respect to HbA(1c) (P<0.05), well-being (P<0.05), diabetes-related distress (P<0.01), frequency of blood glucose testing (P<0.05), avoidance of hypoglycemia (P<0.01), perceived stress (P<0.05), anxiety (P<0.05) and depression (P<0.05), all of which showed greater improvement in the intervention group compared with the control group. A significant difference (P<0.05) was registered with respect to non-severe hypoglycemia, which yielded a higher score in the intervention group. CONCLUSION This CBT-based intervention appears to be a promising approach to diabetes self-management. PRACTICE IMPLICATIONS Diabetes care may benefit from applying tools commonly used in CBT. For further scientific evaluation in clinical practice, there is a need for specially educated diabetes care teams, trained in the current approach, as well as cooperation between diabetes care teams and psychologists trained in CBT.

Acute mental stress impairs insulin sensitivity in IDDM patients

SummaryThe effect of acute mental stress on insulin sensitivity was evaluated in ten IDDM patients, studied on two occasions (test day and control day) in random order and separated by a period of 1–3 weeks. Mental stress was evoked by a modified filmed version of Stroops CWT for 20 min. On the control day, the patients were resting quietly during the corresponding period. Insulin sensitivity was estimated by an insulin (0.4 mU · kg−1 · min−1)-glucose (4.5 mg · kg−1 · min−1)-infusion test (IGIT) for 6.5 h. Mental stress evoked significant responses for adrenaline, cortisol and GH, their respective peak values being 0.27 ± 0.05 nmol/l, 426 ± 27 nmol/l and 7.6 ± 1.8 μg/l, as well as increases in systolic and diastolic blood pressure and pulse rate The steady-state blood glucose levels, i.e. the mean blood glucose levels 3–6.5 h after the start of the IGIT, were significantly higher after stress, compared with those on the control day, 10.6 ± 1.5 vs 8.7 ± 1.4 mmol/l, p = 0.01, demonstrating impairment of the insulin sensitivity by mental stress. It is concluded that acute mental stress induces a state of insulin resistance in IDDM patients, which can be demonstrated by an IGIT to appear 1 h after maximal stress and to last more than 5 h.

Minimal Increases in Glucagon Levels Enhance Glucose Production in Man with Partial Hypoinsulinemia

In man a small dose of somatostatin (50 (μg/h) suppressed moderately basal insulin (5 μU/ml) and glucagon (40 pg/ml) levels. This resulted in a short-lasting hypoglycemia, which was then followed by marginal hyperglycemia throughout the experiment. The addition of a minimal dose of glucagon (0.50 ng/kg/min) to somatostatin normalized basal glucagon levels and resulted in a significant and sustained hyperglycemia. During the first 2 h, hyperglycemia was mainly due to increased glucose production, whereas later on it was maintained by decreased glucose uptake. We conclude that, in man moderately deprived of insulin, even a marginal change in glucagon level induces a long-lasting hyperglycemia.

Atorvastatin has antithrombotic effects in patients with type 1 diabetes and dyslipidemia.

INTRODUCTION Diabetes is a prothrombotic state involving a more thrombogenic fibrin network. In the present study we investigated the effects of lipid-lowering therapy with atorvastatin on fibrin network structure and platelet-derived microparticles in patients with type 1 diabetes and dyslipidemia. MATERIALS AND METHODS Twenty patients were treated with atorvastatin (80 mg daily) or placebo during 2 months in a randomized, double-blind, cross-over study. Fibrin network permeability, expression of glycoprotein IIIa, P-selectin and tissue factor on platelet-derived microparticles, plasma endogenous thrombin potential, plasminogen activator inhibitor-1 and tissue plasminogen activator antigen levels were assessed. Additionally, levels of plasma fibrinogen, high-sensitivity C-reactive protein and glycated haemoglobin were measured. RESULTS During treatment with atorvastatin, fibrin network permeability increased (p=0.01), while endogenous thrombin potential and expression of glycoprotein IIIa, P-selectin and tissue factor decreased (p<0.01). In vitro experiments indicated that platelet-derived microparticles influence the fibrin network formation as fibrin network permeability decreased significantly when platelet-derived microparticles were added to normal plasma. Baseline levels of plasminogen activator inhibitor-1 and tissue plasminogen activator antigen as well as plasma fibrinogen and high-sensitivity C-reactive protein were within reference values and not significantly changed during atorvastatin treatment, while glycated haemoglobin increased 0.3% (p<0.001). CONCLUSIONS Novel treatment effects were found in patients with type 1 diabetes and dyslipidemia during atorvastatin therapy, i.e. a more porous fibrin network, to which reduced expression of glycoprotein IIIa, P-selectin and tissue factor on platelet-derived microparticles may contribute. The observed impairment of glycemic control during long-term statin treatment deserves attention.

Psychosocial state of patients with IDDM prone to recurrent episodes of severe hypoglycemia

Objective The aim of this study was to investigate the psychosocial situation in patients with insulin-dependent diabetes mellitus (IDDM) with recurrent attacks of severe hypoglycemia (SH). Research Design and Methods The study group consisted of 17 adult patients with SH and 17 patients matched to the study group with regard to sex, age, and duration of diabetes without severe attacks. The psychosocial situation was measured by means of self-rated questionnaires and an observers rating scale. Results Parameters such as social support, life events, type A behavior, neuroticism, and vital exhaustion were not different, although a higher anxiety rating (P <0.05) and a lower rating of happiness (P <0.01) were found in the SH group. Conclusions We conclude that the anxiety level is increased and that experienced happiness is decreased in patients prone to recurrent severe hypoglycemia.