Complications of Diabetes Mellitus

Patients with both type 1 and type 2 diabetes are at high risk for the development of chronic complications. Diabetes-specific microvascular pathology in tlie retina, renal glomerulus, and peripheral nerve produces retinopathy, nephropathy, and neuropathy. As a result of these microvascular complications, diabetes is the most frequent cause of new cases of bfindness in the industrialized world in persons between 25 and 74 years and the leading cause of end-stage renal disease.Diabetes is also associated with a marked increase in atherosclerotic macrovascular disease involving 

At the conclusion of the DCCT, 95% of the participants enrolled in the long-term follow-up study, termed the Epidemiology of Diabetes Interventions and Complications (EDIC). Five years after the end of the DCCT, there was no difference in metabolic control (assessed by GHb measure- 

The clinical laboratory has a vital role in both the diagnosis and management of diabetes mellitus. Some of the important parameters assayed are outlined in Table 25-4. In 2002 the National Academy of Clinical Biochemistry (referred to as the NACB) published evidence-based guidelines for laboratory analysis in diabetes mellitus. The guidelines were reviewed by the Professional Practice Committee of the ADA and were consistent in those areas where the ADA also published recommendations. Specific recommendations for laboratory testing based on pubfished data or derived from expert consensus are presented,A brief overview is presented here. 

Type 1 Diabetes. Evidence from animal studies suggests that unmune intervention therapy before the appearance of clinical symptoms can delay or prevent type 1 diabetes. Several large clinical trials are underway to assess a variety of therapeutic strategies designed to delay or prevent the 

Other abnormalities related to cellular dehydration or therapy (Cigii potassium, sodium, phosphate, and osmolality) 

---

It has been proposed that the development of the complications of diabetes mellitus may be linked to oxidative stress and therefore might be attenuated by antioxidants such as vitamin E. Furthermore, it is discussed that glucose-induced vascular dysfunction in diabetes can be reduced by vitamin E treatment due to the inactivation of PKC. Cardiovascular complications are among the leading causes of death in diabetics. In addition, a postulated protective effect of vitamin E (antioxidants) on fasting plasma glucose in type 2 diabetic patients is also mentioned but could not be confirmed in a recently published triple-blind, placebo-controlled clinical trial [3]. To our knowledge, up to now no clinical intervention trials have tested directly whether vitamin E can ameliorate the complication of diabetes. 

The neuromuscular complications of diabetes mellitus are most often neuropathic in origin, with distal sensorimotor polyneuropathies being the most common. In addition, ischemic infarction of skeletal muscle may occur due to occlusive vascular disease, with small and medium-sized arterioles particularly affected. This occurs in poorly-controlled diabetes and affects thigh, muscles in most cases. In acute stages, muscle biopsy findings are those of widespread muscle necrosis, edema, and phagocytic cell infiltration. Muscle regeneration may be incomplete and increased fibrous connective tissue may replace lost muscle tissue. 

Cillery, P., Monboisse, J.C., Maquart, F.X. and Borel, J.P. (1989). Does oxygen free radical increased formation explain long term complications of diabetes mellitus Med. Hypothesis 29, 47-50. 

Sinclair A.J. (1993). Free radical mechanisms and vascular complications of diabetes mellitus. Diabet. Rev. 2, 7-10. 

Foot ulcers and related infections are among the most common, severe, and costly complications of diabetes mellitus (DM). Fifteen percent of all patients with DM develop at least one foot ulcer, resulting in direct health care expenditures of approximately 9 billion annually in the United States.26,27 Diabetic foot ulcers and wounds are highly susceptible to infection. Related skin, soft tissue, and bone infections account for 25% of all diabetes-related hospitalizations.28 More than half of all nontraumatic lower extremity amputations (LEAs) performed each year in Western nations are linked to diabetic foot infection 80,000 LEAs are performed annually in the United States alone.29,30... 

Q7 Ketoacidosis is a serious complication of diabetes mellitus. Because of insulin deficiency and consequent increased availability of fatty acids to the liver, the liver overproduces alpha-hydroxybutyrate and acetoacetic acid, increasing ketone production. The ketones are released into the circulation. They are strongly acidic and, when not effectively buffered, cause metabolic acidosis. Coma may then occur because of severe depression of the nervous system. 

Q8 In type 1 diabetes, because of a lack of insulin, a high level of triglyceride is stored in the liver and can subsequently be converted to phospholipids and cholesterol. Hepatocytes synthesize VLDLs, which can be converted to other types of lipoproteins. These lipoproteins are major sources of cholesterol and triglycerides for most other tissues. They leave the liver, enter the blood and can result in rapid development of vascular atherosclerosis. Increased levels of atherogenic oxidized low-density lipoproteins (LDLs) are seen in hyperglycaemic individuals and contribute to macrovascular disease, which is a complication of diabetes mellitus. 

A number of studies have suggested that vitamin Bg may he effective in preventing the adverse effects of poor glycemic control that lead to the development of the complications of diabetes mellitus (Jain and Lim, 2001). Many of these effects are mediated hy nonenzymic glycation of proteins. Target proteins include the following ... 

Nathan DM. Long-term complications of diabetes mellitus. N Engl J Med 1993 328 1676-85. 

The Amadori sugar-amino acid residue adducts in proteins are produced with prolonged hyperglycemia and undergo progressive nonenzymatic reactions involving dehydration, condensation, and cyclization. These compounds are collectively known as advanced glycosylation end products and are involved in the chronic complications of diabetes mellitus (cataracts and nephropathy) (Chapter 22). 

One of the chronic complications of diabetes mellitus is diabetic nephropathy, which leads to end-stage renal disease. An initial biochemical parameter of diabetic nephropathy in the asymptomatic state is a persistent... 

Honobin DF. The roles of essential fatty acids in the development of diabetic neuropathy and other complications of diabetes mellitus. Prostaglandins Leukotrienes Essential Fatty Acids 1988 44 127-131. 

Reichard P, Nilsson BY, Rosenqvist U. The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus. N Engl J Med 1993 329 304-309. 

Late complications of diabetes mellitus are a result of micro-and macroangiopathies. 

---