B. M. Frier

Hypoglycaemia in insulin‐treated Type 2 diabetes: frequency, symptoms and impaired awareness

Aims  Hypoglycaemia is considered to be less common in people with insulin‐treated Type 2 diabetes than in Type 1 diabetes. A retrospective survey was made of 215 people with insulin‐treated Type 2 diabetes to quantify the frequency and nature of hypoglycaemia experienced.

Frequency and symptoms of hypoglycaemia experienced by patients with type 2 diabetes treated with insulin.

This study ascertained the prevalence of severe hypoglycaemia and loss of awareness of hypoglycaemia in patients with Type 2 diabetes treated with insulin. One hundred and four sequentially selected Type 2 diabetic patients were compared with 104 patients with Type 1 diabetes who were matched for duration of insulin therapy. The patients were interviewed using a standardized questionnaire. During treatment with insulin, 18 Type 2 patients had experienced fewer than two episodes of hypoglycaemia, while 86 had experienced two or more episodes; 80 (93%) reported normal awareness, six (7%) reported partial awareness, and none had absent awareness of hypoglycaemia. All 86 Type 1 diabetic patients matched to the 86 Type 2 patients had experienced multiple episodes of hypoglycaemia; 71 (83%) had normal awareness, 14 (16%) had partial awareness and one patient (1%) reported absent awareness of hypoglycaemia. The Type 1 patients who had altered awareness of hypoglycaemia had longer duration of diabetes and insulin therapy (normal awareness: 5 (1–17) years (median (range)) vs partial awareness: 9 (3–18) years, p < 0.01). Similarly, Type 2 patients with altered awareness had longer duration of diabetes (normal awareness: 11 (2–25) years vs partial awareness: 19 (8–24) years, p < 0.02) and had received insulin for longer (normal awareness: 3 (1–18) years vs partial awareness: 12 (6–17) years, p < 0.001). Severe hypoglycaemia in the preceding year had occurred with a similar prevalence in the Type 2 patients (9 (10%)) and Type 1 patients (14 (16%)), but was more frequent in those patients with partial awareness both in Type 1 patients (normal awareness: 3 (4%) vs partial awareness: 11 (73%), p < 0.001) and in Type 2 patients (normal awareness: 3 (4%) vs partial awareness: 6 (100%), p < 0.001). Although the symptoms of hypoglycaemia were idiosyncratic in individual Type 2 patients, the range and prevalence of specific symptoms were similar to those described by the patients with Type 1 diabetes.

Cardiac function and coronary arteriography in asymptomatic type 1 (insulin-dependent) diabetic patients: evidence for a specific diabetic heart disease.

SummaryCardiac function was examined in 63 asymptomatic Type 1 (insulin-dependent) diabetic patients, aged 30–50 years, using radionuclide ventriculography and exercise electrocardiography to investigate the possible existence of a specific diabetic heart disease. Comparisons were made with 45 age- and sex-matched non-diabetic controls. Radionuclide ventriculography was performed at rest and during the physiological stresses of isometric exercise, cold-pressor testing and dynamic exercise. Scans were technically satisfactory in 56 of the diabetic patients and 38 of the control subjects. The resting left ventricular ejection fractions and the responses to isometric exercise and cold-pressor testing were similar in the diabetic patients and controls. A smaller rise in the left ventricular ejection fraction during dynamic exercise was observed in male diabetic patients compared with male control subjects (9±1% (mean±SEM) vs 14±1% (p< 0.005)). A similar trend was observed in female diabetic patients, with a rise of 5±1% on dynamic exercise compared with a rise of 8 ± 1 % in the control group. Sixteen diabetic patients (29%) demonstrated an abnormal response to dynamic exercise, and 5 of these had an abnormal exercise electrocardiogram. Cardiac catheterisation and coronary arteriography were performed in eight of these 16 patients, and all 8 had normal coronary arteries. Endomyocardial biopsy revealed arteriolar thickening and interstitial fibrosis in 5 patients, and in 2 patients basement membrane thickening was conspicuous. Thus, in diabetic patients cardiac function may be abnormal without evidence of coronary heart disease, and some patients appear to have the histological changes consistent with a diabetic microangiopathy involving the heart.

The effects of insulin-induced hypoglycaemia on cardiovascular function in normal man: studies using radionuclide ventriculography

SummaryThe cardiovascular effects of an intravenous injection of soluble insulin and of acute hypoglycaemia were examined in six normal male subjects using multiple-gated radionuclide ventriculography. The basal left ventricular ejection fraction rose significantly from 47±3% (mean±SEM) to 54±3% p<0.01, within 5 min of the intravenous injection of insulin, and before any significant changes occurred in the blood glucose concentration. The ejection fraction subsequently rose to a peak of 72±5% coinciding with the onset of the acute hypoglycaemic reaction. This corresponded to the nadir of blood glucose and was associated with rises in heart rate, stroke volume and cardiac output. The heart rate returned to the resting value within 30 min of the acute hypoglycaemic reaction, but the ejection fraction, stroke volume and cardiac output were still elevated 90 min later. The peak ejection fraction value immediately preceded the maximal increment of plasma catecholamines released in response to hypoglycaemia. Thus, administration of intravenous insulin had a small, immediate, discernible effect on the cardiovascular system. A subsequent rise in left ventricular ejection fraction of much greater magnitude was stimulated by the development of acute hypoglycaemia, and was associated temporally with sympatho-adrenal activation. The use of radionuclide ventriculography showed that the haemodynamic changes provoked by hypoglycaemia produced a sustained effect on cardiac contractility.

Endomyocardial biopsy pathology in insulin-dependent diabetic patients with abnormal ventricular function

We have previously shown impaired ventricular function in asymptomatic middle‐aged type 1 (insulin‐dependent) diabetic patients who had no evidence of coronary artery disease. The diabetic patients had normal coronary angiograms but reduced ventricular ejection fraction on exercise. To examine the possible contribution of small vessel disease to this functional abnormality, we compared endomyocardial biopsies from seven symptom‐free type 1 diabetic patients with biopsies from seven age‐ and sex‐matched non‐diabetic subjects. Interstitial fibrosis was present in three diabetic patients, arteriolar hyalinization in three patients and arteriolar thickening was observed in five patients. Morphometry performed on electron micrographs showed no significant difference in the thickness of the capillary basal lamina between diabetics and controls. While the functional significance of the abnormalities on light microscopy is unclear, our findings indicate that the abnormality of cardiac function described in diabetes is not associated with thickening of the myocardial capillary basal lamina.

Hypoglycaemia Unawareness in Type 1 Diabetes: A Lower Plasma Glucose is Required to Stimulate Sympathoadrenal Activation

To investigate the relationship between awareness of symptoms and the autonomic reaction of hypoglycaemia, acute hypoglycaemia was induced with intravenous insulin (2.5 mU kg−1 min−1) in diabetic and non‐diabetic subjects, all of whom had normal cardiovascular autonomic function tests. Three groups were studied: (1) nine patients with Type 1 diabetes with loss of awareness of hypoglycaemia; (2) eight patients who had normal awareness of hypoglycaemia, matched for duration of diabetes and blood glucose control; (3) eleven non‐diabetic volunteers. The onset of the acute autonomic reaction was identified objectively by the sudden and rapid responses of heart rate and sweating. Cognitive function and hypoglycaemia symptom scores were estimated serially. Acute autonomic activation was observed to occur in all subjects in response to hypoglycaemia. In the ‘unaware’ diabetic patients, onset of the reaction occurred at a significantly lower plasma glucose (1.0 ± 0.1 mmol l−1) than in the ‘aware’ diabetic patients (1.6 ± 0.2 mmol l−1) (p < 0.05) or in the non‐diabetic control group (1.4 ± 0.1 mmol l−1) (p < 0.05). Obvious neuroglycopenia was observed only in the ‘unaware’ diabetic group and developed when plasma glucose had declined to approximately 1.4 ± 0.1 mmol l−1, and thus preceded the reaction (p < 0.02 vs the autonomic threshold). The maximal rise in plasma adrenaline was of similar magnitude in all three groups but a lower plasma glucose was required to stimulate this hormonal response in the ‘unaware’ patients, in whom the plasma adrenaline concentration was lower at the time of the reaction. Thus, the plasma glucose at which activation of the autonomic reaction was observed was lower in the diabetic patients with unawareness of hypoglycaemia.

Hospital in-patient statistics underestimate the morbidity associated with diabetes mellitus

Hospital in‐patient statistics are an important outcome measurement in the assessment of the morbidity associated with diabetes mellitus. A prospective study of 157 consecutive admissions over a 28‐day period compared diagnoses obtained from the clinical records with the ICD9 coding of the same admissions recorded at the Information and Statistics Division of the Scottish Health Service. Sixty‐one percent of all discharge summaries omitted the diagnosis of diabetes. Even when admission was principally related to diabetes complications, 47% of medical and 88% of surgical discharge summaries omitted diabetes as a diagnostic category. ICD9 coding underestimated the percentage of admissions accounted for by diabetic patients by 100% (2.8 vs 5.6%) and as a result underestimated bed occupancy by over 200% (4.3 vs 13.7%), and is thus failing to fulfil its potential as a demographic and epidemiological record of resource use by disease classification.

Counterregulatory hormonal responses to hypoglycaemia in Type 1 (insulin-dependent) diabetes: evidence for diminished hypothalamic-pituitary hormonal secretion

SummaryAcute insulin-induced hypoglycaemia in humans provokes autonomic neural activation and counterregulatory hormonal secretion mediated in part via hypothalamic stimulation. Many patients with Type 1 (insulin-dependent) diabetes have acquired deficiencies of counterregulatory hormonal release following hypoglycaemia. To study the integrity of the hypothalamic-pituitary and the sympatho-adrenal systems, the responses of pituitary hormones, beta-endorphin, glucagon and adrenaline to acute insulin-induced hypoglycaemia (0.2 units/kg) were examined in 16 patients with Type 1 diabetes who did not have autonomic neuropathy. To examine the effect of duration of diabetes these patients were subdivided into two groups (Group 1: 8 patients < 5 years duration; Group 2∶ 8 patients>15 years duration) and were compared with 8 normal volunteers (Group 3). The severity and time of onset of hypoglycaemia were similar in all 3 groups, but mean blood glucose recovery was slower in the diabetic groups (p<0.01). The mean responses of glucagon, adrenaline, adrenocorticotrophic hormone, prolactin and beta-endorphin were similar in all 3 groups, but the mean responses of growth hormone were lower in both diabetic groups than in the normal group (p<0.05). The mean increments of glucagon and adrenaline in the diabetic groups were lower than the normal group, but these differences did not achieve significance; glucagon secretion was preserved in several diabetic patients irrespective of duration of disease. Various hormonal responses to hypoglycaemia were absent or diminished in individual diabetic patients, and multiple hormonal deficiencies could be implicated in delaying blood glucose recovery. The demonstration of subnormal secretion of adrenaline and pituitary hormones following hypoglycaemia in individual patients supports the concept that central (hypothalamic) activation of counterregulation may be diminished in Type 1 diabetes.

The Effects of Diabetes and Autonomic Neuropathy on Parotid Salivary Flow in Man

Stimulated parotid salivary flow studies were performed on 20 non‐diabetic subjects and on 30 patients with insulin‐dependent diabetes mellitus who had been screened for autonomic neuropathy using tests of cardiovascular reflexes. Electrical gustometry was performed to detect the taste threshold.

Psychological and Demographic Correlates of Glycaemic Control in Adult Patients with Type 1 Diabetes

The relationship between an objective measure of glycaemic control (glycated haemoglobin (HbA1)) and personality variables was examined in two separate groups of adult Type 1 (insulin‐dependent) diabetic patients. Study 1 included 121 patients, all of whom also had subjective self‐reporting of treatment compliance assessed, while the first 57 patients had individual differences in intelligence, major dimensions of personality and forgetfulness documented. Study 2 examined 303 patients, all of whom had their major dimensions of personality assessed using a shortened and updated version of the original personality questionnaire. Demographic indices (age, onset‐age, duration of diabetes) were assessed in both groups. No significant correlation was found between HbA1 and self‐report compliance suggesting that self‐reporting may be invalid as a measure of glycaemic control. In study 1 personality and intelligence variables did not correlate significantly with HbA1 values. Older patients with shorter duration of diabetes had significantly better glycaemic control (p<0.05). A significant correlation was observed between HbA1 concentration and onset‐age of diabetes (p<0.001); the patients who had developed diabetes later in life were achieving better control of their blood glucose. In the larger number of subjects in study 2 no significant correlations were evident between HbA1 and personality variables. It is concluded that the predictors of glycaemic control indexed by HbA1 may be distinct from predictors of self‐report compliance and that the latter have limited or no value in providing an assessment of quality of glycaemic control. There is no evidence of an effect of personality on glycaemic control as measured by HbA1.