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Dietary deprivation  Adult-onset DM

Dietary deprivation  Adult-onset DM. Dietary deprivation  IUGR first described by James Lucas [1794]: advocated “ temperance in diet, a diminution in the usual quantity and a change in the quality of food ” to allow for sub-optimal growth in cases of past CPD.

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Dietary deprivation  Adult-onset DM

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  1. Dietary deprivation Adult-onset DM • Dietary deprivation  IUGR • first described by James Lucas [1794]: advocated “temperance in diet, a diminution in the usual quantity and a change in the quality of food” to allow for sub-optimal growth in cases of past CPD. • Also noted in situations of starvation during wartime: • Leningrad siege [1942] & Netherlands [winter 1944-45] • LBW  Syndrome X [Metabolic syndrome] • NIDDM, hypertension & hyperlipidaemia • Animal experimental models • low protein isocalorific diet causes: • reduced pancreatic beta cell mass -> reduced insulin secretion • insulin target cells programmed to insulin resistance Lumey LH. Pediatric Perinat Epidemiol. 1992 Apr; 6(2): 240-253 DJP. Barker et al: Diabetologia 1993, 36:62-67 J. Petrik et al: Endocrinology 1999, 140:4861-4873

  2. RISK FOR ADULT-ONSET DISEASE [GDM] BY BIRTH WEIGHT “The Laurel and Hardy association” P < 0.05 C. Savona-Ventura & M. Chircop: Acta Diab 2003, 40:101-104 • .

  3. INTRAUTERINE NUTRITION PREDISPOSES TO MACROSOMIA The Brocktorff Family – Nurture factors P << 0.05 P << 0.05 • Gestational diabetes predisposes to Macrosomia • Association has long been identified • Mechanism postulated over 50 years ago by J. Pederson. • Increasing severity makes situation worse suggesting excessive intrauterine nutritional effect P << 0.05 • .. C. Savona-Ventura et al.: Int J Gynecol Obstet, 2003, 82:217-218C. Savona-Ventura, M. Gatt: Int J Diabetes Metabolism, 2006, 14(2):p.88-91

  4. GDM IS A RISK DETERMINANT FOR ADULT-ONSET DISEASE Wizard’s Crystal Ball Metabolic status of Maltese women 8 years postpartum. • … AG. Schranz, C. Savona-Ventura: Exper Clin Endocrinol Diab, 2002, 110:219-222

  5. FAMILY HISTORY RELATIONSHIPS The Brocktorff Family – Nature factors P<<0.05 • Family history statistically linked only to MATERNAL & SIBLINGS • No statistical link to PATERNAL history • Consanguinity did not appear to contribute to an increased risk P<<0.05 P >0.05 - C. Savona-Ventura, AG. Schranz, M. Chircop: Malta Med J, 2003, 15(2):25-27 G. Katona et al, 1983: WHO.NCD/OND/DIAB/83.2

  6. Aetiology - Thrifty phenotype Maternal thrifty fugal restricted diet during pregnancy IUGR causing Fetal Neuro-endocrine changes with reduced pancreatic beta-cell mass ? Genetic Predisposition - Thrifty Phenotype with tendency to Insulin Resistance • . Availability of high fat and refined carbohydrate foods & Obesity ? Gestational DM in pregnancy • .. • . • Hyperinsulinaemia causing • Fetal Pancreatic changes • Hypothalamic changes • DNA changes due to oxidative stress •  Macrosomia • … Type 2 DM in later life

  7. The Maltese Archipelago • Total Area: 316 km2 • Population [1940]: 270755 • agricultural land restriction • Long historical dependence on food imports from Sicily • After declaration of War on Allies by Italy on 11th June 1940, the Islands became isolated and dependant on food stores through convoys via Gibraltar and Alexandria. • Islands heavily bombed; Food shortage lasted until August 1942.

  8. June 1940 – August 1942 • Period of ~900 days • Total of 2537 alerts of air attacks • average: 2.8 alerts per day

  9. Queuing for bread Underground shelters Queuing for water Queuing for vegetables

  10. Increase in infant deaths from congenital debility [dysmaturity] and in maternal deaths from hypertensive disease noted  both situations associated with Intra-uterine growth retardation. • Infant mortality also higher for infectious disease; all other causes of maternal deaths registered lower rates during the war years.

  11. Aetiology - Thrifty Diet phenotype Maternal thrifty frugal restricted diet during pregnancy Placental insufficiency from hypertensive disease Post-War availability of high fat and refined carbohydrate foods  Obesity & Type 2 DM

  12. METHODOLOGY • The study looked at birth weight data of infants born at St. Luke's Hospital during August 1967 – July 1968 to mothers themselves born during the War period [1940-43] and to those born before [1937-39] and after the siege [1944-45]. • During the period under study Total of 1554 births. • After excluding for absent age & birth weight data, macerated stillbirths, twins and premature deliveries; and identifying women born during the 1937-1945 Total of 724 births • 1937-39  167 mothers • 1940-42  243 mothers • 1943-45  314 mothers • Statistical analyses: t-test comparing the differences between the means. Statistical significance identified as a p value <0.05

  13. RESULTS P=0.027 P=0.0005 Maltese women born during the period of the Second World War were more likely to have infants of 3.3-4.2%higher birth weights than women from before and after the conflict.

  14. Every man is some months elder than he bethinks him; for we live, move, have a being and are subject to the actions of the elements and the malice of disease in that other World, the truest Microcosm, the Womb of our Mother. Sir Thomas Brown: “Religio Medici” 1642

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