Can glycaemic variability, as calculated from blood glucose self-monitoring, predict the development of complications in type 1 diabetes over a decade?

AIMS: Is glycaemic variability an independent risk factor for the development of microvascular complications in addition to average glycaemia, as assessed by glycated haemoglobin (HbA(1c))? In this study, an 11-year follow-up was carried out in patients with type 1 diabetes. The standard deviation of blood glucose (SDBG) concentration, an index of glycaemic variability, was calculated from self-monitored blood glucose data at baseline. METHODS: A total of 100 patients were randomly selected from 442 consecutive type 1 diabetic patients attending our outpatients clinic. SDBG was calculated from 70 measurements taken over a period of four weeks. Onset and progression of micro- and macrovascular complications were recorded over the 11-year follow-up. RESULTS: As expected, the prevalence of complications increased over time. Statistical analyses showed that HbA(1c) was an independent predictor of the incidence (P=0.004) and prevalence (P=0.01) of nephropathy. SDBG was found to be a predictor of the prevalence of peripheral neuropathy (P=0.03), and showed borderline significance in predicting the incidence of peripheral neuropathy (P=0.07). SDBG was also a highly significant predictor of hypoglycaemic unawareness (P=0.001). CONCLUSIONS: We conclude that variability of blood glucose may be important in the development of peripheral neuropathy in patients with type 1 diabetes, and that the nervous system may be particularly vulnerable to glycaemic variability.

Follow-up of plasma semicarbazide-sensitive amine oxidase activity and retinopathy in Type 2 diabetes mellitus.

Plasma activity of the enzyme semicarbazide-sensitive amine oxidase (SSAO) is high in diabetes. Production of angiotoxic substances (an aldehyde, hydrogen peroxide, and ammonia) in vessel walls is catalysed by SSAO, suggesting a role for SSAO in the development of complications of diabetes. The objective of the present study was to follow up plasma SSAO activity (measured radiometrically), HbA(1c) (using ion exchange chromatography), and retinopathy (by fundus photography) after 2.8 years, in 34 patients with Type 2 diabetes. We also measured urinary levels of an SSAO substrate, methylamine, by fluorometric high-performance liquid chromatography (HPLC). As at baseline, plasma SSAO activity was now higher in subjects with retinopathy (mean 19.5) than in subjects without retinopathy (mean 16.0), 95% confidence interval (CI) for difference 0.6-6.3 nmol benzylamine ml(-1) plasma h(-1). SSAO activity had not changed significantly since baseline, mean difference -1.65 and 95% CI for difference -3.76 to 0.46 nmol benzylamine ml(-1) plasma h(-1). Mean HbA(1c) level remained higher for patients with retinopathy (now 7.9%) compared to those without retinopathy (6.1%), 95% CI for difference 0.6-3.0%. Comparing baseline and the present study, retinopathy was nonproliferative; level had worsened for five and improved for two patients. Urinary methylamine/creatinine ratio was lower in the group of patients with retinopathy (mean 0.99) than in those without retinopathy (mean 1.78), 95% CI for difference 0.1-1.5 microg mg(-1). The results of the present study are compatible with a role for SSAO in the development of diabetic retinopathy.

Elevated plasma semicarbazide-sensitive amine oxidase (SSAO) activity in Type 2 diabetes mellitus complicated by retinopathy.

AIMS: To measure plasma semicarbazide-sensitive amine oxidase (SSAO) activities and detect retinopathy in Type 2 diabetes mellitus (DM). METHODS: Cross-sectional, population-based study of 65 diabetes patients (61 diagnosed from the age of 30 years) with or without retinopathy as determined by fundus photography in primary care. HbA1c was analysed by ion exchange chromatography on a Mono S for HbA1c column. SSAO activities were assayed radiometrically and formaldehyde-albumin adducts by ELISA in plasma samples from patients and 136 healthy controls. RESULTS: Subjects with diabetes had higher plasma SSAO activity, measured as nmol benzylamine x mlplasma(-11) x h(-1)(mean 20.6), than controls (mean 14.3), P<0.0001; 95% confidence interval (CI) for difference 4.9-7.7. SSAO activity was higher in patients with retinopathy (mean 23.2) than in those without (mean 18.9), P=0.012; 95% CI for difference 1.0-7.5, and related to the HbA1c value. No statistically significant relationship between diabetes duration and SSAO activity was found. With HbA1c values and insulin treatment entered into a multiple logistic regression model, SSAO activity no longer predicted retinopathy, P increasing from 0.025 to 0.17. SSAO activity and the presence of any retinopathy were unrelated to titres of antibodies against formaldehyde-treated human serum albumin. CONCLUSIONS: SSAO activity, earlier found to be elevated in Type 1 DM, is also elevated in Type 2 DM. The SSAO family of enzymes may be involved in the development of diabetic retinopathy, possibly by catalysing the formation of toxic metabolites. A potent and specific inhibitor of human SSAO might help prevent retinopathy in Type 1 and Type 2 DM.

Early detection of diabetic retinopathy by a mobile retinal photography service working in partnership with primary health care teams.

Community-wide fundus photography was organized for early detection of diabetic retinopathy (DR) by mobile teams. High-quality three-field Kodachrome fundus photography, performed according to the London Protocol through dilated pupils was offered free of charge to primary care; images were taken in the community and assessed centrally. Data are presented from the first 80 primary health care centres (PHCCs) participating, serving 990,000 (about 60%) of inhabitants in Stockholm County. Beginning in 1990, 6863 diabetes patients were invited by PHCCs; 5490 (80%) attended. We reached 77% of persons with known diabetes; only 37% had had their eyes examined during the preceding 2 years. For 97% of patients, images were assessable. DR was present in 34% of patients (non-proliferative DR not requiring further assessment 29%, non-proliferative DR requiring further assessment 1.1%, proliferative DR 0.5% and macular involvement 3.6%). Re-examination after 2 years was offered to 64%; follow-up photography after 1 year to 24%. Fluorescein angiography and/or photocoagulation treatment was performed in 3.6%. This method of early diagnosis is feasible, acceptable, and reached twice as many patients as did the usual referral-based system of care. We now plan to extend this service to cover the whole county.

New blindness in diabetes reduced by more than one-third in Stockholm County.

To monitor changes over time in the incidence of blindness among people with diabetes, referrals (mentioning diabetes) to all vision rehabilitation centres in Stockholm County (1995 population 1 725 756) during 1981-1995 were registered. A mass mailing to people with diabetes in 1989 urged them to have their eyes examined. Mobile fundus photography teams initiated early diagnosis of diabetic retinopathy in primary health care in 1990. Referrals with diabetes and blindness, defined (WHO, ICD 10) as best-corrected visual acuity (VA) of the better eye less than 3/60 (0.05), occurred for 172 persons (7.6% of those referred with diabetes). During 1981-1985, 93 were referred (95% confidence interval 75 to 114); 1986-1990, 51 (38 to 67); 1991-1995, 28 (19 to 41). Five-year average annual incidence rate of referrals with blindness was reduced by 47% from 1.2 to 0.63 to 0.33 per 100,000 population. Mean yearly reduction during 1981-1995 was 11% (8 to 15%), 11.5% (8 to 15%) if blindness was defined as in the UK (VA 3/60 or less), and 7% (4 to 9%) for legal blindness (VA 6/60 or less); test for trend p < 0.001 (Poisson regression analysis). This is the first report of reduction in a geographical region of a proxy measure for new blindness in diabetes by one-third or more, attaining one of the main targets of the St Vincent Declaration.

Photographic detection of retinopathy in insulin-treated diabetes. A population study in the city of Tartu, Estonia.

PURPOSE: To perform a cross-sectional baseline investigation of diabetic retinopathy prevalence and metabolic control. METHODS: Using a register of insulin-dependent diabetes mellitus in Tartu (pop. 104,791), 175 patients were invited to fundus photography; 149 (89%) participated, 99 of them diagnosed with diabetes before the age of thirty. Four Kodachrome 64 photographs per eye were taken with a Canon CR4 - 45NM camera through tropicamide-dilated pupils; slides were projected and systematically graded. Capillary blood samples (n = 132) for HbA1c determination were mailed on filter paper. Following cysteine buffer elution, Mono S ion exchange chromatography was performed (reference range 3.7 to 5.3%). RESULTS: Any diabetic retinopathy was found in 114 patients (76.5%; 95% confidence interval, CI, 70 to 83%); mild to moderate non-proliferative retinopathy in 59 (40%; 95% CI 32 to 48%); severe non-proliferative retinopathy in 29 (19.5%; 95% CI 13 to 26%); proliferative retinopathy in 26 (17%; 95% CI 11 to 24%); 47 patients (32%) needed laser photocoagulation. Vitreous haemorrhage was observed in 9 (6%) of subjects. In patients diagnosed with diabetes before the age of 30 years, prevalence of any retinopathy was 82% (95% CI 73 to 89%) and of proliferative retinopathy 23% (95% CI 15 to 33%). Median HbA1c was 9.7% for women and 8.6% for men (95% CI for difference 0.7 to 2.1%). CONCLUSION: Retinopathy prevalences (76-82%) are the highest reported from population-based studies. Glycaemia levels were very high and should be gradually lowered. Methods capable of validation can be successfully introduced for population-based assessment of hyperglycaemia and retinopathy prevalences.