Erik Moberg

Fear of hypoglycaemia in adults with Type 1 diabetes

Diabet. Med. 27, 1151–1158 (2010)

β-Adrenergic regulation of lipolysis and blood flow in human skeletal muscle in vivo

Little is known about the regulation of catecholamine-stimulated lipolysis in human skeletal muscle. Therefore, β-adrenergic regulation of lipolysis and blood flow was investigated in healthy subjects in vivo by use of microdialysis of the gastrocnemius muscle. First, during a hypoglycemic, hyperinsulinemic clamp, which induces a lipolytic response in skeletal muscle tissue, the muscle was locally perfused with β-adrenoceptor blocking agents. Perfusion with nonselective (propranolol) and β2-selective (ICI-118551) blocking agents counteracted the hypoglycemia-induced lipolysis ( P < 0.01), but perfusion with metoprolol (β1-blocker) did not affect the glycerol response. Second, selective β-adrenoceptor agonists were perfused in situ into skeletal muscle during resting conditions. β2-Adrenoceptor stimulation with terbutaline induced a concentration-dependent increase in skeletal muscle glycerol levels and in tissue blood flow, whereas perfusion with β1- or β3-adrenoceptor agonists (dobutamine or CGP-12177) did not influence the glycerol concentration or blood flow. In conclusion, in skeletal muscle tissue, only the β2-subtype is of importance among β-adrenoceptors for regulation of lipolysis and blood flow. This is in contrast to adipose tissue, where β1- and β3-adrenoceptors are also involved.

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.

Fear of hypoglycemia: relationship to hypoglycemic risk and psychological factors

ObjectiveThe major aims of this study were to examine (1) the association between fear of hypoglycemia (FOH) in adults with type 1 diabetes with demographic, psychological (anxiety and depression), and disease-specific clinical factors (hypoglycemia history and unawareness, A1c), including severe hypoglycemia (SH), and (2) differences in patient subgroups categorized by level of FOH and risk of SH.Research design and methodsQuestionnaires were mailed to 764 patients with type 1 diabetes including the Swedish translation of the Hypoglycemia Fear Survey (HFS) and other psychological measures including the Perceived Stress Scale, Hospital Anxiety and Depression Scale, Anxiety Sensitivity Index, Social Phobia Scale, and Fear of Complications Scale. A questionnaire to assess hypoglycemia history was also included and A1c measures were obtained from medical records. Statistical analyses included univariate approaches, multiple stepwise linear regressions, Chi-square t tests, and ANOVAs.ResultsRegressions showed that several clinical factors (SH history, frequency of nocturnal hypoglycemia, self-monitoring) were significantly associated with FOH but R2 increased from 16.25 to 39.2xa0% when anxiety measures were added to the model. When patients were categorized by level of FOH (low, high) and SH risk (low, high), subgroups showed significant differences in non-diabetes-related anxiety, hypoglycemia history, self-monitoring, and glycemic control.ConclusionThere is a strong link between FOH and non-diabetes-related anxiety, as well as hypoglycemia history. Comparison of patient subgroups categorized according to level of FOH and SH risk demonstrated the complexity of FOH and identified important differences in psychological and clinical variables, which have implications for clinical interventions.

Insulin absorption is faster when keeping the infusion site in use for three days during continuous subcutaneous insulin infusion

To evaluate the possible influence of regular infusion site changes on insulin absorption, fifteen type 1 diabetic patients using continuous subcutaneous insulin infusion (CSII) were studied on four occasions: the first day after an infusion site was settled, again the first day after a new infusion site was utilized and the two fourth days after the two infusion sites had been used for three days. A bolus of insulin (1 U/10 kg of body weight) was infused by the pump in the lower para-umbilical region. Plasma free insulin and blood glucose levels were determined before and during 240 min of the study at 30-min intervals. It was found that the peak times extracted from the individual insulin curves were shorter in 17 out of 23 curves when the fourth day was compared with the first day and the mean value of peak time of the fourth day was significantly shorter than that of the first day (56 +/- 11 vs 110 +/- 15 min, P less than 0.01). The mean area under the insulin curves during the first hour of the study tended to increase on the fourth day compared to that of the first day (25 +/- 2.2 vs 21 +/- 2.1 mU.l-1.min, P = 0.12). The decremental area of blood glucose on the fourth day was larger than on the first day (405 +/- 111 vs 82 +/- 160 mmol.l-1.min, P less than 0.05). We conclude that during CSII, the absorption rate of the injected insulin bolus is faster when the infusion site has been in use continuously for three days.

How accurate are home blood-glucose meters with special respect to the low glycemic range?

Comparisons were made between four blood-glucose meters (Diascan, Glucometer II, Reflolux II and ExacTech) and a reference method (YSI) for the full, clinical, blood-glucose range and for the subranges < 4.4 mmol/l, 4.4-10.0 mmol/l and > 10.0 mmol/l, respectively. In the low-glucose range, the error-grid analysis was also applied. All the meters showed acceptable agreement with the reference method when the whole glucose range was considered, yielding r-values between 0.96 and 0.99. However, when the results were separated in the different subranges, the outcome was different, in that the Diascan meter displayed systematically high glucose levels and the ExacTech meter showed a great spread of the values within the low-glucose range, whereas the Glucometer II and the Reflolux II meter were less accurate within the high-glucose range. By applying the error-grid analysis, several errors of clinical importance within the low glycemic range were revealed, while other significant errors, which might lead to inadequate therapeutic decisions, were classified as clinically accurate.

A longitudinal study of fear of hypoglycaemia in adults with type 1 diabetes

To investigate fear of hypoglycaemia (FoH) longitudinally in a cross‐sectional study of adult patients with type 1 diabetes. Specifically, we investigated two subgroups of patients who over 4 years either showed a substantial increase or decrease in level of FoH to identify factors associated with changes in FoH.