BACKGROUND: In circulating lymphocytes of individuals with insulin resistance and overt hyperglycaemia (NIDDM patients), alterations, affecting pyruvate dehydrogenase (PDH), the key enzyme in glucose oxidative breakdown, have been observed. They include below normal enzyme activity and, in vitro, no enzyme response to insulin at low physiological levels (5 m mUaml) as well as activation up to the basal values of controls with insulin at high physiological levels (50 m mUaml), instead of activation and inhibition respectively, as in controls. OBJECTIVE: To investigate whether these alterations characterize circulating lymphocytes of individuals with insulin resistance in whom derangements of glucose homeostasis are absent (obese subjects with normal glucose tolerance), or present but still controllable (nonobese and obese newly diagnosed NIDDM patients on an appropriate diet). SUBJECTS: Thirty obese subjects (BMI 36 AE 3) responding normally to an oral glucose tolerance (OGT) test; 60 newly diagnosed NIDDM patients (30 nonobese, BMI 22 AE 4 and 30 obese, BMI 38 AE 2); 30 nonobese (BMI 21 AE 5) and nondiabetic subjects, with no family history for NIDDM, served as controls. METHODS: Evaluation of PDH activity in circulating lymphocytes before and after exposure to insulin at 5 and 50 m mUaml, and of clinical parameters before and during an OGT test. RESULTS: 1) In circulating lymphocytes of obese nondiabetic subjects as well as obese and nonobese newly diagnosed NIDDM patients, PDH activity was signi®cantly below normal. In vitro, enzyme response to insulin at 5 m mUaml was reduced in nonobese NIDDM patients with respect to controls, and absent in obese nondiabetic subjects and obese NIDDM patients. Enzyme response to insulin at 50 m mUaml was reversed in all individuals, which allowed enzyme activity to recover up to the basal level of controls. 2) In NIDDM patients and obese nondiabetic subjects, undergoing an OGT test, the area under the glycaemic curve (g-AUC) was as expected; the area under the insulinaemic curve (i-AUC) was increased in both groups with respect to controls, but signi®cantly only in the latter. CONCLUSION: In individuals with insulin resistance PDH activity in their circulating lymphocytes rises up to basal levels of controls, only if these cells are exposed to insulin at high physiological concentrations, and g-AUC is normal only in those subjects who have signi®cantly increased i-AUC. This suggests that with insulin at suf®ciently high concentrations both parameters can be corrected. We conclude that the derangements responsible for the alterations of the two parameters share common features and thus the described PDH alterations in circulating lymphocytes re¯ect systemic insulin resistance whether accompanied by hyperglycaemia or not.

Patients' health perceptions and internal control mechanisms may be insufficiently developed for optimal participation in retinopathy screening. Diabetes care by long-term group education may address this problem.

Aims/hypothesis Most guidelines recommend annual screening for diabetic retinopathy (DR) but limited resources and the slow progression of DR suggest that longer recall intervals should be considered if patients have no detectable lesions. This study aimed to identify the cumulative incidence and time of development of referable DR in patients with no DR at baseline, classified by clinical characteristics.Methods Analysis was performed of data collected prospectively over 20 years in a screening clinic based in a teaching hospital according to a consensus protocol. The cumulative incidence, time of development and relative risk of developing referable retinopathy over 6 years following a negative screening for DR were calculated in 4,320 patients, stratified according to age at onset of diabetes (<30 or ≥30 years), being on insulin treatment at the time of screening and known duration of diabetes (<10 or ≥10 years). Results The 6 year cumulative incidence of referable retinopathy was 10.5% (95% CI 9.4, 11.8). Retinopathy progressed within 3 years to referable severity in 6.9% (95% CI 4.3, 11.0) of patients with age at onset ≥30 years, who were on insulin treatment and had a known disease duration of 10 years or longer. The other patients, especially those with age at onset <30 years, on insulin and <10 years duration, progressed more slowly. Conclusions/interpretation Screening can be repeated safely at 2 year intervals in any patient without retinopathy. Longer intervals may be practicable, provided all efforts are made to ensure adherence to standards in procedures and to trace and recall non-attenders.

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