A LATERAL VIEW OF DIABETES FROM THE CARIBBEAN. Part I

A LATERAL VIEW OF DIABETES FROM THE CARIBBEAN The Hon. Errol Y. St. A. Morrison, OJ MD, PhD, FRCP (Glasg), FACP, FRSM (UK) Professor of Biochemistry and Endocrinology Pro Vice Chancellor and Dean School for Graduate Studies and Research UNIVERSITY OF THE WEST INDIES Mona Campus, Jamaica W.I. THE WORLD THE CARIBBEAN AND CENTRAL AMERICA Hugh Jones 1955 Zuidema 1956 Morrison 1981 Atypical Diabetes; Undernutrition; Bush teas (CAM) & Staple root crops Atypical Diabetes - hyperglycaemic & aglycosuric - asymptomatic hyperglycaemia - intermittent insulin requirement - aketonuric - 13% of Diabetes Outpatient Clinic at UHWI, Mona, Jamaica Francis Bacon If a man will begin with certainties, He shall end in doubts; But if he will be content to begin with doubts, He shall end in certainties! AN HYPOTHESIS FOR THE AETIOLOGY OF DIABETES MELLITUS FREE RADICALS FOOD “TOXINS”, UNDERNUTRITION AN HYPOTHESIS FOR THE AETIOLOGY OF DIABETES MELLITUS (contd.) FR DAMAGE TO CELL MEMBRANE Level 1 AN HYPOTHESIS FOR THE AETIOLOGY OF DIABETES MELLITUS (contd.) DAMAGE TO CELL MEMBRANE VIRAL INFECTIONS EXPOSED ANTIGENS INDUCED ANTIGENS AN HYPOTHESIS FOR THE AETIOLOGY OF DIABETES MELLITUS (contd.) EA Level 2 IA ANTIBODIES DIRECT TOXICITY INSULIN RECEPTORS GLUCOSE TRANSPORTERS ISLET CELLS AN HYPOTHESIS FOR THE AETIOLOGY OF DIABETES MELLITUS (contd.) OBESITY Level 3 IR GT IC INSULIN RESISTANCE INSULIN INSUFFICIENCY AN HYPOTHESIS FOR THE AETIOLOGY OF DIABETES MELLITUS (contd.) INSULIN RESISTANCE INSULIN INSUFFICIENCY TYPE 2 NON-INSULIN DEPENDENT DIABETES MELLITUS PIDDM PHASIC INSULIN DEPENDENT DIABETES MELLITUS TYPE 1 INSULIN DEPENDENT DIABETES MELLITUS AN HYPOTHESIS FOR THE AETIOLOGY OF DIABETES MELLITUS (contd.) Level 1: Membrane damage Level 2: Antibody production Level 3: Insulin resistance & insufficiency AN HYPOTHESIS FOR THE AETIOLOGY OF DIABETES MELLITUS (contd.) N.B.: If the processes at levels 1, 2 or 3 remit, then TEMPORARY DIABETES would result! AN HYPOTHESIS FOR THE AETIOLOGY OF DIABETES MELLITUS (contd.) N.B.: GESTATIONAL DIABETES (GDM) IMPAIRED GLUCOSE TOLERANCE (IGT)……possible manifestations of level 3 activity. The Unitarian Hypothesis THE UNITARIAN HYPOTHESIS FOR THE AETIOLOGY OF DIABETES MELLITUS HERESY TODAY? FACT TOMORROW! CONSENSUS ON THE AETIOLOGY OF TYPE 2 DIABETES MELLITUS SRI LANKA, JULY 2002 OVERNUTRITION  Increase in type 2 DM in childhood and adolescence UNDERNUTRITION  Low birth weight  increase in type 2 DM CONSENSUS ON THE AETIOLOGY OF TYPE 2 DIABETES MELLITUS (contd.) There is a strong association between:  Truncal Obesity    Diabetes Mellitus Impaired Glucose Tolerance Cardiovascular Disease Hugh Jones 1955 Zuidema 1956 Morrison 1981 Atypical Diabetes; Undernutrition; Bush teas (CAM) & Staple root crops ROOT CROPS a case study. CYANOGLUCOSIDES E.g. Linamarin, lotaustralin (toxic cyanide radical) Found in root crops: Cassava, yucca (Manihot esculenta), Yams (Dioscorides group) CASSAVA (manihot esculenta) YAM (Dioscorides GROUP) YAM (Dioscorides GROUP) ENZYMATIC DEGRADATION OF LINAMARIN MAIN METABOLIC PATHWAY OF CYANIDE WITH RHODANESE S E S + (S —SO3) 2- E S —S —SO3 S CN rhodanese thiosulphate S E S + SO 2 + SCN 3 - thiocyanate METABOLIC PATHWAY OF CYANIDE WITH 3 - MERCAPTOPYRUVATE TRANSAMINATION L – CYSTEINE [SHCH2CH(NH2)COOH] 3 MERCAPTOPYRUVATE [HSCH2COCOOH] CN – SULPHUR TRANSFERASE SCN + PYRUVATE Louis Pasteur Chance favours the prepared mind!