Diabetes and CVD

A prospective study of cardiovascular disease in patients with Type 2 diabetes 6.3 years of follow-up.

(Journal of Diabetes and its complications (2003)17: 235-242.)

Critique and a Mauritian approach

by Rehana Jauhangeer and Pamela Greenwell

Molecular and Medical Microbiology Research Group

University of Westminster

London W1 W 6UW.

Many studies have found that Type 2 diabetes mellitus (T2DM) is an important risk factor for cardiovascular disease (CVD). This study carried out by Riu et al. (2003) has found that there is a low incidence of CVD in Spanish patients with T2DM. As the title suggests, the patients were followed for about six years.

In all, 176 T2DM patients were studied who at baseline were without CVD. The cohort was composed of 63% women and 37% men. Biological data were collected every six months. Several parameters were recorded including diabetic retinopathy, systolic arterial pressure, HbA_1C urinary albumin excretion rate (UAER), glomerular filtration rate (GFR) and total cholesterol. The patients had been chosen on the basis of a family history of T2DM, CVD and hypertension.

Results show that 16% of the patients suffered from CVD for the first time. These events were in accordance to the diagnosed hypertension, presence of retinopathy and nephropathy, levels of HbA_1Cand total cholesterol at baseline. During follow-up, an association between HbA_1C, cholesterol, urinary albumin excretion, glomerular filtration rate and systolic arterial pressure and CVD has been noted. Furthermore, the appearance or deterioration of diabetic retinopathy or nephropathy, creatinine and UAER increase, decrease of GFR and effective renal plasma flow has been associated with CVD events during follow-up. However, an independent association has been observed between CVD and mean HbA_1C, mean UAER and the presence of proliferative diabetic retinopathy at baseline.

The conclusions reached for this study are that there is a low incidence of CVD in the Spanish patients and that there is an independent relationship between the appearance of CVD and the level of HbA_1C, the level of UAER and the presence of diabetic retinopathy at baseline.

Joslin stated in 1927 that “ I believe the chief cause of premature development of atherosclerosis in diabetes, save for advancing age, is an excess of fat, an excess of fat in the body, an excess of fat in the diet, and an excess of fat in the blood” (Valabhji & Elkeles 2003).

In 1975-1977, the World Health Organisation initiated an international study in order to observe the variations in the occurrence of the different forms of vascular diseases in insulin-dependent and non-insulin-dependent diabetes (Fuller et al. 1996). The study was carried out in five European centres, two East Asian centres, two Native American centres and one Caribbean centre. There was a large variation between the centres in ischaemic heart disease and cerebrovascular disease mortality for both insulin-dependent and non-insulin-dependent diabetes. The lowest mortality rate from cardiovascular diseases was observed in diabetics in Tokyo and Hong Kong. However, high blood pressure and proteinuria were identified as cardiovascular risk factors in diabetics.

In 1999, the UK Prospective Diabetes Study (UKPDS) found that 59% of newly diagnosed diabetics died from cardiovascular diseases (Adler et al.). Today, it is also known that there is acceleration in atherosclerosis in diabetics (Nesto & Rutter 2002). Patients with T2DM have lipid abnormalities that are characterised by high levels of triglycerides and low density lipoprotein (LDL) cholesterol and by low level of high density lipoprotein- cholesterol (HDL-c). Thus the patients with T2DM have a two-to-six fold greater risk of mortality from cardiovascular diseases than normal individuals (Valabhji & Elkeles 2003). Thus, it is important that accurate lipid and lipoprotein measurements be made.

The control of pre-analytical factors as well as biological variation should be considered for the reliable assessment of coronary heart disease risk and for the management of dyslipidaemia (Richmond 2003). In the study carried out by Riu et al. (2003), the lipid measurements were performed partly manually and by automated equipment. The manual step may have introduced some random errors to the determination of the lipids.

Riu et al. (2003) also found that there is an independent relationship between T2DM and its metabolic control and Coronary Heart Disease (CHD). However other studies carried out by Kuusisto et al. (1994) and Gall et al. (1995) found that T2DM and its metabolic control represented by the level of HbA1c are important factors that will predict CHD.

In 1993, a study carried out by Tuomiletho et al. in Mauritius suggests that the prevalence of T2DM as well as the mortality from CHD was highest in the world. The patients in this study were men and women aged 35-74 and they were of different ethnic groups namely Asian Indians (Hindus and Muslims), Creoles and Chinese. The results showed that there is an association between diabetes and glucose intolerance with CHD in Mauritians and this was largely due to hypertension. Furthermore, hyperglycaemia, hypertension and lipid abnormalities have been shown to form part of the “metabolic syndrome” in Mauritius (Boyko et al. 2000).

Interestingly, a study was carried out by Francke at al. in Mauritius in 2001, where 99 Indo-Mauritian families were studied with a view to perform a genome-wide scan to map the locus of the gene that is linked with CHD in diabetic patients. The families were ascertained through a proband that died from angina before the age of 52. The analysis showed that there was a linkage with markers on chromosome 3 and chromosome 16 that were related to CHD and /or myocardial infarction. This study also showed that there is a linkage with markers on chromosome 8 with T2DM. These regions harbour some potential candidate genes and could be the basis for future genetic studies.

In the UK, in the UKPDS study, the patients were on an intensive treatment for hypertension and hyperglycaemia. However, their lipid levels did not improve but the results of this study has provided enough information for the future management of diabetic patients with dyslipidaemia. The current management of diabetic dyslipidaemia emphasises on the lowering of the LDL cholesterol (Betteridge 2001). The major studies that have been carried out recently have led to the recommendation that HMG-CoA reductase inhibitors (statins) be used as first choice drug therapy to reduce lipids in diabetic dyslipidaemia by the American Diabetes Association and Joint European Task Force. Other trials are using antihypertensive therapy with angiotensin-converting enzyme inhibitors and calcium channel blockers (Scott 2002). It is only at the end of these trials that the efficacy of these drugs will be known.

References:

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Fuller, J.H, Stevens, L.K & Wang, S.L. (1996). (Abstract) International variations in cardiovascular mortality associated with diabetes mellitus: the WHO Multinational Study of Vascular Disease in Diabetes. Ann Med 28: 319-322.

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Riu, F.R, Vert, I.S, Martin, A.L, Gonzalez, R.R & Sala, A.S. (2003). A prospective study of cardiovascular disease in patients with Type 2 diabetes 6.3 years of follow-up. Journal of Diabetes and its complications 17: 235-242.

Scott, R (2002). Answering the unanswered questions: ongoing trials of statins and antihypertensives in type 2 daibetes. Acta Diabetologica, 39: s46-s51.

Tuomilehto J, Li, N, Dowse, G, Garreboo, H, Chitson, P, Fareed, D, Min, Z, Alberti, K.G.M.M, Zimmet, P. (1993). The prevalence of coronary heart disease in the multi-ethnic and high diabetes prevalence population of Mauritius. Journal of Internal Medicine, 233: 187-194.

Valabhji, J & Elkeles, R.S. (2003). Dyslipidaemia in Type 2 Diabetes: Epidemiology and Biochemistry. Br J Diabetes Vasc Dis 3: 184-189.