Late diabetic complication

With time, the increased glucose concentration leads to glycosylation of the proteins over Amadori products to advanced glycosylation products (AGEs) and cross-linking between proteins. This degenerative process leads to the so-called late diabetic complications (LDC) after some decades. The four main complications are ... 

An increasing number of type 2 diabetic subjects are treated with insulin, including insuhn analogues. At present, there is no hard end point on mortality, morbidity or late diabetic complication, indicating the superiority of analogue insulins compared with conventional insulin treatment. HbAlc, fasting plasma glucose, postprandial... 

Mohamed, AK Bierhaus, A Schiekofer, S Tritschler, H Ziegler, R Nawroth, PP. The role of oxidative stress and NF-kappaB activation in late diabetic complications. Glucose or diabetes activates, fi/q/ijrcioro, 1999 10(2-3) 157-67. 

In practical daily life it is important to establish near normoglycaemic control in the all patients with diabetes mellitus, which means a FtbAlc of <6.5% to reduce the risk for patients being affected by late diabetic micro- and macro-vascular complications. This will in most patient mean a rather intensive treatment and at least more intensive than present where average HbAlc are far above in most regions of the world. 

Under diabetic conditions, oxidative stress and endoplasmic reticulum stress are induced in various tissues [173, 176, 177, 178, 179]. Moreover, the y9-cells have very low levels of antioxidative enzymes, becoming them more susceptible to the stress [172]. ROS can function as signaling molecules to activate a number of cellular stress-sensitive pathways that cause cellular damage, and are ultimately responsible for the late complications of diabetes. Evidence suggests that common stress-activated signaling pathways such as nuclear factor nuclear factor-xB (NF-kB) [180, 181, 182], p38 mitogen-activated protein kinase (MARK) [183], protein kinase C (PKC) [184], toll-like receptors (TLRs) [185, 186], and c-Jun N-terminal kinase (INK) [187 188] underlie the development of these diabetic complications. 

Renal insufficiency is a late complication of hypertension (354). This is why the choice of the antihypertensive drug selected as the firs (dine treatment of a condition that will persist for many years is so important. From this viewpoint, the fall in blood pressure induced by ACE inhibitors might have beneficial renal effects, in addition to those induced by any decrease in perfusion pressure of the kidneys, especially in diabetic patients (222, 355-358). It is unknown if, independendy of the hemodynamic effect, at an early stage of hypertension and before the initiation of a progressive decrease in renal function, a local decrease in angiotensin II (or increase in bradykinin) explains or direcdy participates in a so-called renoprotective effect (359). 

Many experts believe that treating insulin resistance in the prediabetic state or after type 2 diabetes has become manifest may prevent or delay the development and progression of type 2 diabetes (111). Because insulin resistance is an underlying factor in P-cell failure and in other concomitants of type 2 diabetes such as obesity, dyslipidemia, and hypertension, early resolution of insulin resistance in the at-risk population may also reduce critical cardiovascular risk factors and thus prevent the development of late arterial and renal complications (115). 

A characteristic problem with diabetes is the large span of time-scales involved. Metabolic experiments usually last a few hours and only address one particular pathway. The nutrient traffic involves time-scales of hours to days or weeks, but the development of late complications takes years or decades. It is therefore important to analyze the experimental results and place them in a greater context to see which effect a modification of the pathway in question will have on the overall progression of the disease. 

Pancreatic diabetes is usually a late manifestation that is commonly associated with pancreatic calcification. Ketoacidosis, vascular complications, and nephropathy are uncommon with this form of diabetes. 

Wang PH, Lau J, Chalmers TC. Meta-analysis of effects of intensive blood-glucose control on late complications of type I diabetes. Lancet 1993 341 1306-1309. 

Being sedentary is a risk factor for diseases such as heart attack and late-onset diabetes. One-third of adult Americans are obese, perhaps as much the result of cheap gasoline as the plentiful supply of food.47 Obesity-related complications result in 300,000 premature deaths in the United States each year. This is less of a problem in most other countries. For example, the incidence of obesity in the United Kingdom is 15-16.5%. 

Clinical microvascular complications are seen late in the course of diabetes, but attempts to relate the degree of microangiopathy to the prevail-... 

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