Wednesday, 27 October 2010
Diabetes in Cambodia.. Another Explanation
Cambodia 30 years Later..
Foetal Origins of Adult Disease
The Barker Hypothesis
A leading Academic Nephrologist was once asked: is there a physiological explanation for the susceptibility of renal disease among the native populations?
It is possible that they have a lesser number of nephrons, 800 000 per kidney rather than the usual one million, which may predispose them to later kidney disease.
In the kidney, maternal dietary imbalance may lead to developmentally induced deviations from the optimal ratio of body mass to nephron number. A relative deficiency in the number of nephrons is thought to create an increased risk of inadequate renal function and hypertension in later life31,53 and, ultimately, a predisposition to renal failure and a potentially reduced life span.54 The severity of the hypertension in rodent models appears to depend on sex, with males having higher risk.43 The molecular mechanisms are incompletely understood. In the rat, the intrarenal renin–angiotensin system appears to be critical for normal nephrogenesis and may be altered by maternal dietary imbalance, both during the neonatal stage55 and at later time points.56
There is no doubt in my mind that Renin Angiotensin System is important, from a clinical stand point. One is able to protect the life of the individual by protecting the kidney by Angiotensin Converting Enzyme Inhibition ( such as Lisinopril, Enalapril )
Other studies have implicated reduced activity of the antiapoptotic homeobox gene product paired box 2 (Pax-2) in reduced number of nephrons57,58
The propensity of all native peoples: American Indians, Australian Aboriginals, Polynesians could be a genetic protective or genetic modified mechanism.
In all hunting and gathering societies, the intake of meat was sporadic but when it did occur, large amounts of meat were eaten. It is well known that meat, products from the meat, increases renal flow and that an expansion of existing glomerular filtration would become necessary, thus a decreased number of nephrons could balloon themselves periodically to accommodate the sporadic event. When the sporadic events become regular, as the native communities adjust to a European Diet, there may be weakening of this mechanism, leading to a propensity for renal dysfunction ( this is just my theory!)
or have suggested that hypertension in later life caused by maternal dietary imbalance results from up-regulated sodium transport in the distal nephron, possibly triggered by increased oxidative stress.59
the Normal Blood pressure is a point of contention. The current 130/90 was formulated by Insurance Actuaries in Connecticut, and is possibly suited for Europeans, even that I am not sure. Certainly Asians and indigenous people have a normal BP readings in the range of 120/70 and we should aim at that. Overweight possibly is the single most common reason for an increase of BP of about 5 mm Hg.
Nutritional stress in pregnant rats reduces the growth of the endocrine pancreas during organogenesis and increases beta-cell apoptosis,60 leading to hyperglycemia and impaired insulin secretion when the offspring become adults. Glucocorticoids may be involved in inducing phenotypic changes and have been shown to inhibit the transcription factor pancreatic and duodenal homeobox 1 (Pdx-1) in beta-cell precursors, which may affect the resultant number of beta cells.61 In the adult male rat offspring of mothers on a protein-restricted diet, low birth weight is associated with reduced expression of components of the insulin signal-transduction pathway in skeletal muscle (including the protein kinase C zeta isoform, the p85 regulatory subunit of phosphoinositide-3 kinase, and the insulin-sensitive glucose transporter type 4 [GLUT4]).62 Similar abnormalities have been reported in infants of low birth weight,62 and together with the developmentally induced reduction in skeletal muscle mass,3 these abnormalities might contribute to later insulin resistance.
I have seen a number of cases, of young men presenting with Hyperglycaemia, who are thin and presentation mistaken for Type 1 Diabetes. Unlike ketosis prone Type 2 Diabetes, these young people do not revert to normal or not able to get by using oral hypoglycaemic agents.
Review of the histories of these patients revealed two common features:
Intra Uterine Pancreatic Insult
Adult Pancreatic Insult.
Both with excessive alcohol.
It is possible that the intrauterine pancreas were insulted with alcohol and stunted ( other chemicals possibly could do the same), and limping by the glucostasis when further insult to the pancreas decrease their ability to maintain homeostasis of Glucose.
In the rat model of nutritional imbalance, the offspring of rats fed an imbalanced diet during pregnancy later had elevated blood pressure, reduced nephron number, and increased responses to salt loading55 as well as reduced vasodilator function in the systemic arteries.40 Rat pups subjected to hypoxic conditions during gestation appear to have fewer but larger cardiomyocytes than pups exposed to normal oxygen levels and are more susceptible to infarction during periods of ischemia and reperfusion as adults.63 Increased blood pressure in fetal sheep stimulates cardiomyocytes to leave the cell cycle prematurely and hypertrophy,64 which may affect cardiac function in adult life. Cardiac hypertrophy is also evident in lambs born to ewes undernourished during early gestation.65 Chronic fetal anemia alters the developing coronary vascular tree in the near-term sheep fetus, and the remodeled coronary tree persists into adulthood.66 In one study, carotid intima–media thickness at 9 years of age in 216 children of European ancestry whose mothers had energy intake in the lowest quartile during early or late pregnancy was higher than that of children whose mothers had intake in the highest quartile, a finding that implies that maternal nutrition within an unexceptional range during pregnancy can affect the subsequent risk of atherogenesis in the offspring.67
THE ABOVE INFORMATION IS OF EXTREME IMPORTANCE FOR THOSE WORKING IN THE FIELD OF DIABETES IN CAMBODIA. I WOULD LIKE A SOCIAL COMMENTARY OF THE SITUATION DURING THE ERA 30 YEARS AGO, DETAILING THE NUTRITIONAL DEFICIENCIES TO BE ADDED TO THIS.
I BELONG TO A GROUP OF PEOPLE WHO SIXTY FIVE TO SEVENTY YEARS AGO UNDERWENT A MOST BRUTAL HOLOCAUST KNOWN IN EUROPE. WE REMEMBER IT AS SHOAH..
The term holocaust originally derived from the Greek word holókauston, meaning a "completely (holos) burnt (kaustos)" sacrificial offering to a god. Its Latin form (holocaustum) was first used with specific reference to a massacre of Jews by the chroniclers Roger of Howden and Richard of Devizes in the 1190s. Since the late 19th century, it has been used primarily to refer to disasters or catastrophes.
The biblical word Shoah (שואה) (also spelled Sho'ah and Shoa), meaning "calamity," became the standard Hebrew term for the Holocaust as early as the 1940s. Shoah is preferred by many Jews for a number of reasons, including the theologically offensive nature of the original meaning of "holocaust
HOWEVER PAINFUL IT MAY BE, IT IS IMPORTANT TO REMEMBER..