Diabetes, type overt

Chavers BM, Bilous RW, EUis EN, Steffes MW, Mauer SM. Glomerular lesions and urinary albumin excretion in type I diabetes without overt proteinuria. 

Williams ME, Bolton WK, Khalifah RG, Degenhardt TP, Schotzinger RJ, and McGill JB. Effects of pyridoxamine in combined phase 2 studies of patients with type 1 and type 2 diabetes and overt nephropathy. Am J Nephrol, 27 605-614 (2007). 

Strong mechanistic evidence from rodent models of autoimmune disease of viral or other infectious agents affecting autoimmunity or progression to overt disease, but harder to demonstrate in humans. Enterovirus (Coxsackie virus) focus of epidemiologic studies in type 1 diabetes, Epstein-Barr virus focus of epidemiologic studies in multiple sclerosis and systemic lupus erythematosus. 

Diabetes mellitus causes about 50% of all patients being treated for End Stage Renal Disease (ESRD) in the USA and this is because the disease (type 2 disease) is pervasive. Recent studies have shown that the onset and progression of the disease can be ameliorated if treatment is instituted early on in the course of the disease. ESRD is the commonest complication of type 1 diabetes. A higher proportion of individuals with type 2 diabetes was found to have microalbuminuria and overt nephropathy shortly after the diagnosis of diabetes, because the diabetes had actually been present for many years before the diagnosis was made. There is a correlation between the degree of albuminuria and cardiovascular disease. 

In the adult population, the prevalence of overt hypothyroidism is 19 per 1000 women and 1 per 1000 men with annual incidence of overt hypothyroidism is 4 per 1000 women and 0.6 per 1000 men. Subclinical hypothyroidism is also more common in women, the incidence increases with age, with up to 10% of women older than 60 years having an increased thyroid-stimulating hormone concentration. Subclinical hypothyroidism is more common in people who have been treated for hyperthyroidism with radioactive iodine or surgery, and in those with organ-specific autoimmune diseases, such as pernicious anaemia, type 1 diabetes mellitus, or Addison s disease. 

Yasuda G, Hasegawa K, Kuji T, et al. Effects of doxazosin on ambulatory blood pressure and sympathetic nervous activity in hypertensive type 2 diabetic patients with overt nephropathy. Diabet Med. 2005 22 1394-1400. 

Autoimmune mechanisms are blamed for the destruction of pancreatic p cells in overt type 1 diabetes. The exact means, however, by which this selective destruction occurs in humans is unknown (Atkinson and Maclaren, 1994). In order to gain an insight into the human disease, various animal models have been developed and extensively studied the often investigated one being the non-obese diabetic (NOD) mouse (Atkinson and Leiter, 1999). 

Treatment with either vanadium salts or organic complexes of vanadium have decreased plasma insulin levels and improved insulin sensitivity in animal models of both insulin resistance and type 2 diabetes. This work has recently been reviewed [13]. The Zucker Diabetic Fatty (ZDF) rat develops overt hyperglycemia in the presence of hyperinsulinemia followed by [3-cell depletion. This is a type 2 diabetic rat model developed from the Zucker Fatty (fa/fa) rat. In these animals, chronic treatment with vanadium reduced the elevated plasma glucose levels [152,153], The effect in the type 2 models of diabetes can take weeks to develop, whereas the effect in the type 1 models of diabetes are seen within 3 to 4 days. 

Aside from glomerulonephritis, the impact of solvent exposure in other renal diagnoses needs to be explored. Indeed, it is of particular note that all these studies are limited to the former type of renal disease while the role of hydrocarbons in the other renal diagnoses such as diabetic nephropathy should be considered [27, 28]. Interestingly in this context is the recent observation by Nuyts et al. [28] in a group of patients with diabetic nephropathy where hydrocarbon exposure was found in 39% of the patients with that particular type of renal disease. This corroborates the results of Yaqoob et al. [27] who found higher exposure scores to hydrocarbons in patients with incipient (odds ratio 4.0) and overt (odds ratio 5.8) diabetic nephropathy as compared to diabetic individuals without clinical evidence of nephropathy. 

Rossing P, Hougaard P, Parving HH Riskfactorsfordevelopment of incipient and overt diabetic nephropathy in type 1 diabetic patients a 10-year prospective observational study. Diabetes Care 25 859-864,2002. 

Type-I diabetes is the result of an immunologically mediated genetically programmed destruction of the B-cells. This process may require many years and can be documented by several humoral and cellular immunological abnormalities preceding the clinical onset of the disease. Islet cell surface antibodies (ICA) and insulin autoantibodies (IAA) are often detected years before overt clinical symptoms start. A florid insulitis, however, has mainly been observed only close to the time of diagnosis (Bottazzo et al., 1985). 

The onset of the autoimmune disease Type-I diabetes has a protracted prodromal period. Overt symptoms such as hyperglycaemia occur only months and years after initial metabolic and immunological abnormalities such as impaired glucose tolerance, ICA and IAA are noted. 

The presence of increased UAE denotes an increase in the transcapfilary escape rate of albumin and is therefore a marker of microvascuiar disease. Persistent UAE greater than 20p.g/min represents a twentyfold greater risk for the development of clinically overt renal disease in patients with type 1 and type 2 diabetes. Prospective studies have demonstrated that increased UAE precedes and is highly predictive of diabetic nephropathy, end-stage renal disease, cardiovascular mortality, and total mortahty in patients with diabetes mel-litus. The DCCT and UKPDS showed that intensive diabetes therapy can significantly reduce the risk of devel-... 

If the confirmatory test result is positive, treatment witli an ACE inhibitor or angiotensin-receptor blocker should be initiated. ACE inhibitors delay the progression to overt nephropathy, and the National Kidney Foundation recommends their use in both normotensive and hypertensive type 1 and 2 diabetic patients. The role of monitoring UAE in patients on ACE inhibitor therapy is less clear, although many experts recommend continued surveillance. Untreated, the UAE would increase 10% to 30% per year, whereas the albumin creatinine ratio in patients on ACE inhibitors should stabilize or decrease by up to 50%. 

There is ongoing controversy as to whether intensive glucose therapy alone can prevent progression of incipient to overt nephropathy. Other factors, such as lowering blood pressure and blockade of ACE and All, are important. High blood pressure accelerates the progressive increase in albuminuria in patients with initially normal urinary albumin excretion and accelerates loss of kidney function in those with overt nephropathy in type 2 diabetes. A subgroup analysis of the Swedish Hypertension Optimal Trial (HOT)... 

Type 1 diabetes, which represents the diagnosis for 5 to 10% of the diabetic population, is oaused by an absolute deficienoy in insulin secretion. This overt absence of insulin produotion results from immune system-mediated destruction of the insulin-producing pancreatic 3 cells. Without insulin, the body s primary source of energy and the brain s only source of energy, glucose, is unable to ... 

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