Robert Tattersall

Infusion of pramlintide, a human amylin analogue, delays gastric emptying in men with IDDM

Summary Pramlintide, a human amylin analogue, reduces hyperglycaemia after meals in patients with insulin-dependent diabetes mellitus (IDDM). We investigated whether this was due to delayed gastric emptying. Eight men with uncomplicated IDDM were studied twice in a randomised, double-blind crossover design. Euglycaemia was maintained overnight by intravenous infusion of glucose and/or insulin and the following morning a 5-h infusion of pramlintide 25 μg/h or placebo was started at 08.00 hours. At 08.30 hours the patients injected their normal morning insulin dose subcutaneously and 30 min later ate a meal (600 kcal, 50 % carbohydrate) of which the solid component was labelled with Technetium-99 m and the liquid with Indium-111 to quantify gastric emptying. Gamma-scintigraphic images were obtained every 20 min for the next 4 h. Insulin and glucose were infused as necessary to maintain blood glucose levels within 3 mmol/l of the pre-meal value. Compared to placebo, pramlintide significantly delayed emptying of both liquid (median lag time 69 vs 7.5 min) and solid (median lag time 150 vs 44.5 min) components of the meal. Pramlintide delayed gastric emptying so much that t50 values could not be calculated for solid or liquid. Amylin agonists such as pramlintide may, therefore, be of value in improving glycaemic control in IDDM by modifying gastric emptying. [Diabetologia (1997) 40: 82–88]

Insulin-induced hypoglycaemia in an accident and emergency department: the tip of an iceberg?

In one year a prospective survey in a large accident and emergency department identified 204 admissions of adults with severe hypoglycaemia, 200 in insulin-treated patients. Ninety-six had one admission while 34 others were admitted on 104 occasions. Of the 130 patients, 111 attended diabetic clinics in Nottingham, forming 9% of a known clinic population of 1229 on insulin treatment. Since many other episodes of hypoglycaemia were presumably treated outside hospital, 9% a year is a minimum estimate of the incidence of severe hypoglycaemia in our area. The mean insulin dose was 1.2 units/kilogram/day for those admitted twice or more and 0.9 U/kg/day for those admitted once; these doses were significantly higher than those of an age-matched clinic population. A year after the latest admission with hypoglycaemia, the mean insulin dose in the group with two or more admissions had fallen to 0.8 U/kg/day, suggesting that over-treatment had been an important causal factor. A similarly high incidence has been reported in other studies, and we believe that it is due mainly to the inadequacy of conventional subcutaneous insulin treatment.

Alcohol causes hypoglycaemic unawareness in healthy volunteers and patients with Type 1 (insulin-dependent) diabetes

SummaryBoth hypoglycaemia and alcohol consumption affect cognitive function but it is unclear whether moderate drinking alters awareness of hypoglycaemia. We have examined this in a single blind randomised hyperinsulinaemic clamp study in eight non-diabetic subjects and seven Type 1 (insulin-dependent) diabetic patients. After 30 min of euglycaemia (blood glucose 4.5 mmol/l) subjects drank either 0.75 g/kg ethanol or a placebo drink after which blood glucose was lowered to 2.5 mmol/l for 40 min. Awareness of hypoglycaemia, reaction time and physiological responses were measured before and after ethanol. At a blood glucose concentration of 4.5 mmol/l, ethanol (producing peak blood levels of 20–25 mmol/l) caused a transient increase in systolic blood pressure (p<0.05), a sustained increase in heart rate (p<0.01) and a slowing of reaction time in both normal subjects and diabetic patients. During hypoglycaemia in both groups, the slowing of reaction time and increase in sweating were more marked after ethanol than placebo (both p<0.05), while the increase in finger tremor (p<0.05) was blunted after ethanol, in both groups. Counter regulatory hormone secretion was not affected by ethanol. Despite increases in symptoms during hypoglycaemia, only 2 of 15 individuals “felt hypoglycaemic” after ethanol compared to 11 out of 15 after placebo. We conclude that after moderate drinking non-diabetic subjects and Type 1 diabetic patients are less aware of hypoglycaemia despite exaggerated physiological changes.

Home blood glucose monitoring

ConclusionDoctors find it impossible to stabilize and monitor diabetic patients in hospital without measuring blood glucose levels and it seemed logical that patients would also manage themselves better if they were able to measure blood glucose during their ordinary life. The development of glucose oxidase sticks and Reflectance meters has made this possible. Six groups have published their experience with home blood glucose monitoring in 188 patients. All have found that patients have little difficulty in obtaining blood samples and can get accurate results. When patients measure blood rather than urinary glucose they understand the disease better and become more motivated. Control has been greatly improved in the majority of patients and some can maintain normoglycaemia for long periods of time. Cheaper and more portable machines will make the method more widely applicable. Both HbA1c and home blood glucose monitoring will be increasingly used in the management of the insulin-taking diabetic since they provide complementary information.

Group Education for Obese Patients with Type 2 Diabetes: Greater Success at Less Cost

It has been suggested that much effort expended in teaching diabetic diets is ineffective and wasteful. We have tested a different system by randomly allocating 75 newly diagnosed obese Type 2 diabetic patients to usual ‘unstructured’ clinic care or to group education by diabetes specialist nurses and a dietitian. Patients allocated to group education attended five 90‐min group sessions during the first 6 months. Six months after diagnosis they had lost more weight (median (95 % CI), 7 (5.5–9) vs 2 (1–5) kg, p<0.002) and were better controlled (HbA1: 7.5 (7.0–8.1) vs 9.5 (8.7–10.4) %, p<0.001) than those randomized to the usual clinic system. At 1 year (after no further visits) the difference in weight loss was less (5.5 (4–6.5) vs 3 (2–4) kg, p<0.05) and diabetic control was similar (HbA1:9.0 (8.2–9.8) vs 9.9 (8.9–10.9) %. At 1 year only 14 (39 %) of the education group and 9 (23 %) of those attending the clinic had a fasting blood glucose less than 7.0 mmol l−1.

In search of the Somogyi effect.

Insulin-treated diabetic patients may show a rapid swing to hyperglycaemia after episodes of hypoglycaemia. This rebound hyperglycaemia, or Somogyi effect, is thought to be caused by the unopposed actions of hormonal antagonists to insulin secreted in response to hypoglycaemia. To test this theory a study was made of 15 patients who had 17 episodes of asymptomatic untreated hypoglycaemia (blood-glucose less than 2 mmol/l) between 11 P.M. and 3 A.M. After nocturnal hypoglycaemia, mean fasting blood-glucose concentrations at 7 A.M. ranged from 0.7-17 mmol/l and were over 7 mmol/l in 6 patients. These 6 patients with apparent rebound hyperglycaemia did not have higher levels of growth hormone, cortisol, or glucagon than those who had little or no recovery of blood-glucose. There was a close inverse correlation (r = -0.996, p < 0.001) between blood-glucose and free insulin, suggesting that hyperglycaemia, when present, was due to relative insulin deficiency in the latter part of the night. Early changes in blood-glucose after untreated hypoglycaemia seem to be primarily due to changes in free insulin rather than a response to antagonist hormones.

Diabetes in the elderly — a neglected area?

ConclusionsMy intention has been to suggest that there are enough subtle differences between diabetes in the old and that in young to make management of the former a speciality in its own right. Elderly patients with diabetes are likely to have not only complications of the disease but also other complicating diseases. To avoid adding iatrogenic complications requires a good knowledge of applied pharmacology as well as a carefully-designed treatment plan with a single named individual in overall charge. Many old people perceive diabetes as a matter of little concern [47] so that those looking after them must be especially diligent.

Well-Being, Cerebral Function, and Physical Fatigue After Nocturnal Hypoglycemia in IDDM

OBJECTIVE This study assessed the effect of nocturnal hypoglycemia on well-being cerebral function, and physical fatigue the next day in 10 subjects with IDDM. RESEARCH DESIGN AND METHODS After an exercise test to determine work-loads corresponding to 30 and 60% VO2max, volunteers were studied twice, 4 weeks apart. Blood glucose was lowered one night to 2.3–2.7 mmol/l for 1 h, and at the control visit, hypoglycemia was avoided. The next morning, well-being was assessed using the minor symptom evaluation profile (MSEP), and cerebral function was assessed with the paced auditory serial addition test, the digit symbol substitution test, trail making part B, four-choice reaction time, and auditory P300 latency. Subjects then exercised at predetermined workloads corresponding to 30% VO2max for 30 min and 60% VO2max until exhaustion. Fatigue was assessed every 10 min using the Borg scale for rating of perceived exertion. RESULTS All three components of the MSEP scored higher (indicating more symptoms) after the hypoglycemic night compared with the control night (P < 0.01 contentment, sleep; P < 0.001 vitality). None of the cerebral function tests performed the next day was affected by hypoglycemia. Exercise capacity was similar at both visits, but subjects were more fatigued after the hypoglycemic night (P < 0.01, analysis of variance). There were no differences in potassium, catecholamine, glucose, or lactate concentrations between visits either before or during exercise. CONCLUSIONS One hour of hypoglycemia at night affects a subjects sense of well-being, but not cerebral function, the next day. The greater fatigue after the hypoglycemic night cannot be explained by the biochemical parameters measured.

Gastric emptying in diabetes.

Gastric emptying abnormalities are common in diabetic patients but correlate poorly with gastrointestinal symptoms. Poor diabetic control is more likely to lead to gastrointestinal complications of diabetes and the converse is also true. Gastric emptying may be a previously under‐recognized contributor to variations in glycaemic control in diabetes. There is evidence for both accelerated and delayed gastric emptying. More rapid gastric emptying would result in higher postprandial glucose levels and, therefore, pharmacological means to delay the rate of gastric emptying may be a new approach to slowing postprandial nutrient absorption and improving diabetic control. Hyperglycaemia reduces the rate of gastric emptying in both Type 1 (insulin‐dependent) and Type 2 (non‐insulin‐dependent) diabetic patients. The exact mechanisms responsible for the inhibitory action of hyperglycaemia on gastric emptying are unknown. There is insufficient data on the effect of hypoglycaemia on gastric emptying but one study has reported more rapid gastric emptying.

Double-Blind Evaluation of Efficacy and Tolerability of Metformin in NIDDM

Objective To test the efficacy and tolerability of metformin. Research Design and Methods An 8-mo double-blind placebo-controlled parallel-group trial was performed at University hospital diabetic clinics on 60 patients with non-insulin-dependent diabetes mellitus (NIDDM) treated by diet alone. Metformin was administered and built up to a maximum dosage of 1 g three times daily. Results Mean HbA1 fell from 11.7 ± 0.4 to 10.3 ± 0.4% (means ± SE) on metformin but rose from 11.8 ± 0.4 to 13.3 ± 0.4% on placebo (P <0.001). Final mean fasting blood glucose was 5.1 mM lower with metformin than placebo (P <0.001). No other biochemical variable differed significantly, and weight did not change. A favorable glycemic response was not restricted to the obese. The mean final dosage of metformin was 1.7 ± 0.1 g and was well tolerated. Conclusions Metformin achieved a 23% lower mean HbA1 than placebo without weight gain or significant unwanted effects.