The incidence of diabetes mellitus in an English community: a 20-year follow-up of the Whickham Survey.

The original Whickham Survey documented the prevalence of diabetes and lipid disorders in a sample of 2779 adults aged 18 years and over, which matched the British population structure. The aim of the 20-year follow-up study was to determine the incidence and natural history of diabetes. Outcomes in terms of morbidity and mortality at follow-up were determined in over 97% of the original population. Ninety-four subjects had been identified and treated for diabetes since the first survey, including 17 subjects identified as having a fasting plasma glucose > or = 7.8 mmol l-1 at follow-up. The incidence of diabetes for the total population was 2.2 1000-1 year-1 (95% confidence interval 1.8, 2.6). The risk factors identified at first survey were corrected for age, cut-off at the 95 centile and entered into a log linear model. Those which strongly predicted development of diabetes in the total population were fasting blood glucose (odds ratio (OR) (with 95% confidence intervals) = 2.3 (1.5, 3.5)) and body mass index (OR = 2.2 (1.5, 3.3)) in men, and fasting blood glucose (OR = 2.6 (1.7, 4.1)) and fasting serum triglyceride (OR = 2.8 (1.8, 4.4)) in women. A logit model has enabled the calculation of the probability of developing diabetes 20 years later. It was the characteristics of becoming older such as obesity, hypertriglyceridaemia, and raised fasting blood glucose, rather than age itself, which were associated with the development of diabetes.

The development of ischemic heart disease in relation to autoimmune thyroid disease in a 20-year follow-up study of an English community.

The original Whickham Survey documented risk factors for cardiovascular disease and the prevalence of thyroid disorders in a sample of 2779 adults that closely matched the British population. A 20-year follow-up study has determined outcomes in terms of morbidity and mortality from ischemic heart disease in over 97% of the original survey population. Analysis of deaths from all causes and from ischemic heart disease showed no association with antithyroid antibody status identified at first survey. A multiple logistic regression using the development of ischemic heart disease in the total population at follow-up as the dependent variable found that the significant predictor variables for men were age, cholesterol, mean arterial blood pressure, smoking history, and skinfold thickness index. For women only age, cholesterol, and mean arterial blood pressure were significant. The presence of autoimmune thyroid disease, as defined by either hypothyroidism, positive antithyroid antibodies, or raised serum thyrotropin at first survey, was not significant. A retrospective cohort study of a subsample of women identified at first survey with positive antithyroid antibodies or raised serum thyrotropin and closely matched controls found no significant association with mortality or development of ischemic heart disease. There is no evidence from this study to suggest that evidence of autoimmune thyroid disease identified 20 years ago is associated with an increased risk of ischemic heart disease.

The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey.

BACKGROUND AND OBJECTIVE: The original Whickham Survey documented the prevalence of thyroid disorders in a randomly selected sample of 2779 adults which matched the population of Great Britain in age, sex and social class. The aim of the twenty-year follow-up survey was to determine the incidence and natural history of thyroid disease in this cohort. DESIGN, PATIENTS AND MEASUREMENTS: Subjects were traced at follow-up via the Electoral Register, General Practice registers, Gateshead Family Health Services Authority register and Office of Population Censuses and Surveys. Eight hundred and twenty-five subjects (30% of the sample) had died and, in addition to death certificates, two-thirds had information from either hospital/General Practitioner notes or post-mortem reports to document morbidity prior to death. Of the 1877 known survivors, 96% participated in the follow-up study and 91% were tested for clinical, biochemical and immunological evidence of thyroid dysfunction. RESULTS: Outcomes in terms of morbidity and mortality were determined for over 97% of the original sample. The mean incidence (with 95% confidence intervals) of spontaneous hypothyroidism in women was 3.5/1000 survivors/year (2.8-4.5) rising to 4.1/1000 survivors/year (3.3-5.0) for all causes of hypothyroidism and in men was 0.6/1000 survivors/year (0.3-1.2). The mean incidence of hyperthyroidism in women was 0.8/1000 survivors/year (0.5-1.4) and was negligible in men. Similar incidence rates were calculated for the deceased subjects. An estimate of the probability of the development of hypothyroidism and hyperthyroidism at a particular time, i.e. the hazard rate, showed an increase with age in hypothyroidism but no age relation in hyperthyroidism. The frequency of goitre decreased with age with 10% of women and 2% of men having a goitre at follow-up, as compared to 23% and 5% in the same subjects respectively at the first survey. The presence of a goitre at either survey was not associated with any clinical or biochemical evidence of thyroid dysfunction. In women, an association was found between the development of a goitre and thyroid-antibody status at follow-up, but not initially. The risk of having developed hypothyroidism at follow-up was examined with respect to risk factors identified at first survey. The odds ratios (with 95% confidence intervals) of developing hypothyroidism with (a) raised serum TSH alone were 8 (3-20) for women and 44 (19-104) for men; (b) positive anti-thyroid antibodies alone were 8 (5-15) for women and 25 (10-63) for men; (c) both raised serum TSH and positive anti-thyroid antibodies were 38 (22-65) for women and 173 (81-370) for men. A logit model indicated that increasing values of serum TSH above 2mU/l at first survey increased the probability of developing hypothyroidism which was further increased in the presence of anti-thyroid antibodies. Neither a positive family history of any form of thyroid disease nor parity of women at first survey was associated with increased risk of developing hypothyroidism. Fasting cholesterol and triglyceride levels at first survey when corrected for age showed no association with the development of hypothyroidism in women. CONCLUSIONS: This historical cohort study has provided incidence data for thyroid disease over a twenty-year period for a representative cross-sectional sample of the population, and has allowed the determination of the importance of prognostic risk factors for thyroid disease identified twenty years earlier.

Diabetes care in general practice: an approach to audit of process and outcome.

As a chronic condition in which the major adverse outcomes only occur after many years, diabetes poses special problems for continuing medical audit. The feasibility of continuous audit of process and outcome in diabetes care has been tested in four general practices with organized diabetes care in Newcastle upon Tyne. For all patients with previously diagnosed non-insulin dependent diabetes, the data already collected according to published protocols were assembled into a single database. The time and resource costs of this exercise, together with measures of process, complications, risk factors, and metabolic outcomes were analysed. Data were successfully collected at minimal cost where structured records were completed. Recommended processes had been completed in a high percentage of patients, adverse patient outcomes were limited, and metabolic output measures not unsatisfactory. Nevertheless, attention has been directed to areas where care could be improved. Continuing diabetes audit in primary health care is feasible and helpful, and can use the same measures as in the hospital setting.

Does flexibility at mealtimes disturb blood glucose control on a multiple insulin injection regimen?

Randomized crossover studies of a half-sized lunch with reduced insulin dose in 21 patients, and a delayed (by 2 h) evening meal in 22 patients, compared with normal meals, were performed in Type 1 diabetic patients. The aim was to examine whether the size and timing of meals can be varied in patients on multiple injection regimens without disturbance of blood glucose control. All patients had previously had their control optimized on multiple injection therapy using a pen-injector. The studies were carried out at home on 6 days (3 changed meals, 3 control) over 2 months, and as 8- and 7-h metabolic profiles (1 study day, 1 control) in an investigation unit. A halved calorie lunch with half the usual insulin dose resulted in equivalent blood glucose control on the study day (area under curve: changed meal 40.0 +/- 3.4 vs control meal 40.3 +/- 3.5 mmol l-1 h for the 5-h period after the meal). Ketone body levels were also unchanged. The late evening meal shifted the post-prandial blood glucose concentration accordingly, but the excursion was not different in extent from the control day (24.8 +/- 1.9 vs 21.0 +/- 1.7 mmol l-1 h). A small excursion of 3-hydroxybutyrate levels before the delayed meal (to 187 +/- 48 mumol l-1) was quickly corrected on eating. Hypoglycaemia was not different in frequency on the changed meal days. Thus no problems of clinical significance were observed when some flexibility in meal size and timing was allowed.

A comparison of human ultralente- and lente-based twice-daily injection regimens.

The problem of fasting hyperglycaemia remains unresolved on currently used twice-daily injection regimens. Human ultralente insulin is of longer duration than human lente and differs from it only in the nature of the zinc-insulin complex. In a 6-month double-blind crossover study these insulins were compared in 66 patients who were randomized to human ultralente or human lente insulin given together with human soluble insulin in a twice-daily injection regimen. Patients were seen monthly and crossed over after 3 months treatment. Fasting blood glucose concentrations on the ultralente regimen were considerably lower than on the lente regimen, the difference being statistically significant (6.6 +/- 0.5 vs 8.2 +/- 0.5 mmol l-1, p less than 0.05), but only present in those patients with fasting concentrations below the median. Glycosylated haemoglobin was identical on both regimens (9.3 +/- 0.2%). The evening ultralente dose was slightly but significantly lower than the evening lente dose (14.9 +/- 0.8 vs 15.5 +/- 0.8 U, p less than 0.05) thus endorsing the lowering effect of ultralente on the fasting blood glucose concentration. However, the incidence of serious hypoglycaemic events was higher on the ultralente regimen (0.38 +/- 0.10 vs 0.09 +/- 0.04 events per patient-month, p less than 0.02), the majority of nocturnal events occurring between 0500 h and breakfast. We conclude that ultralente insulin can give an improved fasting blood glucose concentration but that in those patients with more marked fasting hyperglycaemia or with a nocturnal hypoglycaemia problem it offers no clinical advantage over human lente insulin in a twice-daily injection regimen.

Double-blind crossover trial of isophane (NPH)- and lente-based insulin regimens.

Isophane (NPH) and lente insulin preparations have been the basis of insulin-injection regimens for many decades but were never formally compared. After a 2-mo run-in period, 82 patients were randomized to NPH (Protaphane) or lente (Monotard) insulin preparations given together with Actrapid as a twice-daily injection regimen in a double-blind study. Patients were seen monthly and crossed over after 5 mo of treatment. Control as assessed by glycosylated hemoglobin (NPH 9.2 +/- 0.1%, lente 9.3 +/- 0.1%, mean +/- SE) and fructosamine (1.55 +/- 0.02 and 1.57 +/- 0.02 mM) concentrations was identical for the two regimens as were home-collected laboratory-measured fasting blood glucose (BG) (NPH 8.8 +/- 0.5 mM, lente 9.0 +/- 0.5 mM) and mean BG (8.2 +/- 0.3 and 7.6 +/- 0.3 mM) concentrations. For both regimens, the major control problem was the BG concentration before and after breakfast. Total insulin dosage was similar (NPH 56.3 +/- 0.6 U/day, lente 57.2 +/- 0.6 U/day) with no tendency for a difference in the evening intermediate-acting dose (NPH 17.0 +/- 0.3 U/day, lente 17.0 +/- 0.3 U/day) to counter fasting hyperglycemia. Serum lipid concentrations and body weight confirmed the equivalence of control. Hypoglycemic events were recorded in personal diaries and graded by predetermined criteria. Self-treated, relative-assisted, and hospital/doctor-treated hypoglycemic events did not differ in frequency. We conclude that lente- and NPH-based twice-daily human insulin regimens give indistinguishable metabolic control.

Insulin treatment: a decade of change.

Insulin treatment is still heavily constrained by the problems of inappropriate absorption profiles from subcutaneous tissue, and variability of that absorption. While human insulin may be slightly disadvantageous in these respects, and its possibly lower antigenicity of little clinical consequence, it does provide assured supply. Insulin syringes remain the basis of injection therapy, but pen injectors (yet to be subjected to formal clinical trial) should increase in popularity because of patient convenience, if pens containing complexed insulin prove safe. Nevertheless insulin regimens are still dependent on the extended-acting preparations for basal insulin supply. These preparations remain too short-acting and erratically absorbed to achieve optimum blood glucose control. While insulin analogues are awaited, the promise of insulin pumps and other routes of administration, as means of overcoming these problems, looks to be unfulfilled in the near future.