Medicine Newbie: Diabetes mellitus

Friday, 28 September 2012

Diabetes mellitus

Discovery of insulin

One of the great stories from medical history is Banting and Best's visit to the terminal ward where children with juvenile-onset diabetic coma went to die. The two went down the line of children injecting insulin. As they were finishing, the first children injected were already awake. Insulin was available in 1922 from Eli Lilly and Company. Eli Lilly was a chemist. Best assisted Captain Banting. Collip assisted Macleod. Macleod and Banting won the 1923 Nobel Prize for Physiology or Medicine. Each then shared their prize with their assistants. Sir Frederick Grant Banting died during WWII in 1941 and was buried in Mt Pleasant in Toronto, Canada.

Pancreatic disease
http://www.pathguy.com/lectures/pancreas.htm

Diabetic problems

Gallstones (made of cholesterol; nobody knows why these are more common in diabetics, but the average gallbladder volume is much higher in non-insulin-dependent diabetics, perhaps promoting stasis and nidation: Dig. Dis. Sci. 43: 344, 1998.)
Altered platelet function (significance?)
Complications of pregnancy -- all the common problems are commoner in diabetic mothers, and babies are bigger (partly the hyperglycemia, probably partly some growth factor or other: Br. J. Ob. Gyn. 103: 427, 1996) and at extra risk for a variety of birth defects (all of which seem to be preventable by euglycemia through pregnancy).
Diabetic xanthomas (yellow skin bumps -- pseudotumors made of lipid-laden macrophages), necrobiosis (focal necrosis of the dermis), and many other skin abnormalities
Infections (bacterial and fungal) -- Why diabetics get more infections is still poorly-understood. Candida may thrive on the glucose, hyperglycemia slows down polys, poor circulation keeps the body from fighting infection, etc., etc.).
Babies of diabetic mothers have hyperplastic islets (because of all that glucose), and they are infiltrated with lymphocytes and eosinophils (mysterious.)
Eyes -- Diabetes is the commonest cause of blindness before old age in the US. Review: Lancet 350: 197, 1998. Cataracts: a variety of types, including some clearly caused by sorbitol deposition (proof Proc. Nat. Acad. Sci. 9: 2780, 1995; remains a robust finding). Glaucoma: reason for its being more common with diabetes is uncertain. Diabetic retinopathy: the most serious diabetic eye problem (Lancet 376: 124, 2010)
Kidneys -- The etiology of diabetic glomerulopathy is complex and poorly-understood. Intrarenal fluid dynamics are involved. We don't even know why the kidneys enlarge in diabetics (NEJM 324: 1662, 1991, still good). Tight control of blood glucose does seem to benefit these patients, and reduces the hyperfiltration response to amino acids (NEJM 324: 1629, 1991). Patients are now put on ACE-inhibitors and protein-restricted to prevent progression of the renal disease. (Yes, it can regress due to therapy: NEJM 348: 2285, 2003). Ace-inhibitor plus a calcium channel blocker works marvellously to prevent diabetic kidney disease: NEJM 351: 1941, 2004. Renal lesions in diabetes: Thick tubular basement membranes (not a health problem). Fatty change of tubular cells (systemic lipid disturbance, not a health problem). Glycogen in proximal tubular cells (Armanni-Ebstein lesion, a sign of heavy glycosuria, not itself a health problem). Lots of glycogen in the tubular cells. Kidney infections (gram-negative bacilli causing infection of renal pelvis in pyelonephritis, staphylococci causing cortical infections, candida infections, etc.) Sometimes present: "Fibrin caps" ("exudative lesion", "hyperfiltration lesion") -- hyaline frosting on a glomerular tuft; "Capsular drops" -- hyaline material on the inside surface of Bowman's capsule (highly characteristic of diabetes.) Clinically, patients have albuminuria (rarely heavy proteinuria), then renal failure (probably due to the mesangium crunching the glomerular capillaries). Renal papillary necrosis -- just like it sounds. The lesion is seen in diabetes, obstruction, sicklers, Wegener's, or abuse of the analgesic phenacetin.)