Per-Eric Lins

Efficacy and Safety of Mexiletine in the Treatment of Painful Diabetic Neuropathy. The Mexiletine Study Group

OBJECTIVE To investigate the efficacy and safety of mexiletine in the treatment of painful diabetic neuropathy. RESEARCH DESIGN AND METHODS A total of 216 insulin-treated diabetes patients with painful diabetic neuropathy were randomly allocated to three dosages of mexiletine or placebo. The Visual Analog Scale (VAS) for pain/discomfort was scored each day during daytime and nighttime, and sleeping disturbances were also recorded by the patients. Plasma levels of mexiletine and 24-h electrocardiogram (ECG) mapping were assessed before and during the 3-week study period. RESULTS A significant reduction in sleep disturbances and pain during nighttime was observed in the group of patients taking the highest dosages (675 mg/day) of mexiletine compared with the other groups. No significant correlation was found between plasma concentration of mexiletine and the therapeutic effect or adverse events. No serious adverse events were seen. The 24-h ECG mapping did not disclose onset of significant arrhythmias in any patient. CONCLUSIONS Mexiletine in a dosage of 675 mg daily can reduce pain caused by diabetic neuropathy, and the effect of this drug appears to have a rapid onset.

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.

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.

Inhibitory Effect of Circulating Insulin on Glucagon Secretion During Hypoglycemia in Type I Diabetic Patients

Objective –To clarify whether the circulating insulin level influences hormonal responses, glucagon secretion in particular, during hypoglycemia in patients with insulin-dependent (type I) diabetes. Research Design and Methods –Nine type I diabetic patients were studied. During two separate experiments, hypoglycemia was induced by low-dose (244 pmol.kg−1.h−1) and high-dose (1034 pmol.kg−1.h−1) intravenous insulin infusions for 180 min in each case. The arterial blood glucose level was directly monitored every 1.5 min, and glucose was infused in the high-dose test to clamp the arterial blood glucose level to be identical as in the low-dose test. Results –Despite the fact that the plasma insulin level was four times higher in the high-dose than in the low-dose test (740 ± 50 vs. 180 ± 14 pM), a close to identical arterial hypoglycemia of ∼ 3.3 mM was obtained in the two experiments. During hypoglycemia, a significant rise of the plasma glucagon level was found only in the low-dose test (188 ± 29 vs. 237 ± 37 ng/L, P < 0.05), and the incremental area under the glucagon curve was significantly greater in the low-dose than in the high-dose test (140 ± 19 vs. −22.7 ± 34 ng/L.h−1, P < 0.005). The responses of plasma epinephrine, norepinephrine, growth hormone, pancreatic polypeptide, and somatostatin were similar in both tests and, consequently, were not significantly modified by the circulating insulin level. Conclusions –This study demonstrates that, in type I diabetic patients, the glucagon response to hypoglycemia is suppressed by a high level of circulating insulin within the physiological range. Our findings may help to explain the impairment of glucagon secretion during hypoglycemia frequently seen in these patients.

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.

Placental hormones during induced hypoglycaemia in pregnant women with insulin-dependent diabetes mellitus: evidence of an active role for placenta in hormonal counter-regulation.

Objective To study the effect of induced hypoglycaemia on serum levels of the placental hormones oestriol, human placental lactogen, placental growth hormone and progesterone in the third trimester of pregnancy.

Psychometric evaluation of the Swedish version of the Hypoglycaemia Fear Survey

OBJECTIVE The objective of this study was to evaluate the psychometric properties of the Swedish version of the Hypoglycaemia Fear Survey (Swe-HFS) for use among Swedish-speaking patients with type 1 diabetes. METHODS The HFS was translated using the forward-backward translation method and was thereafter answered by 325 type 1 patients. The psychometric properties were investigated using exploratory factor analysis, Cronbachs alpha, content and convergent validity. RESULTS The factor analysis showed that a three-factor solution was reasonable with the subscales Behaviour/Avoidance (10 items), Worry (6 items) and Aloneness (4 items). Cronbachs alpha coefficient for the total score was 0.85. The result also supports the instruments content validity and convergent validity. CONCLUSION The Swedish version of the HFS appears to be a reliable and valid instrument for measuring fear of hypoglycaemia (FoH) in type 1 patients. PRACTICE IMPLICATIONS The results from this study suggest that the Swe-HFS, an instrument that is brief and easy to administer, may be valuable in clinically assessing FoH among patients with type 1 diabetes.

Impaired endothelium-dependent skin microvascular function during high-dose atorvastatin treatment in patients with type 1 diabetes

Aims: The present study investigated the effects of lipid-lowering therapy with atorvastatin on skin microvascular function in patients with type 1 diabetes and dyslipidaemia. Methods: Twenty patients received daily treatment with atorvastatin 80 mg or placebo during 2 months in a randomised, double-blind, cross-over study. Forearm skin microcirculation was investigated with laser Doppler perfusion imaging during iontophoresis of acetylcholine and sodium nitroprusside to assess endothelium-dependent and endothelium-independent microvascular reactivity, respectively. Various biochemical markers of endothelial function were also investigated. Results: Endothelium-dependent microvascular reactivity decreased during atorvastatin (p < 0.001), showing a significant treatment effect compared with placebo (p = 0.04). Atorvastatin treatment was also associated with increased haemoglobin A1C levels from 7.45% to 7.77% (p = 0.008). Conclusions: The present study shows impaired endothelium-dependent skin microvascular function during high-dose atorvastatin treatment in patients with type 1 diabetes, thus implicating a risk for deterioration of microvascular function during such therapy in these patients.