World Diabetes Day

I’ve added a countdown to the sidebar for Diabetes Day, November 14. This is the primary global awareness campaign of the diabetes world. Introduced by the International Diabetes Federation (IDF) and the World Health Organization (WHO), World Diabetes Day was created due to concern over the increasing cases of diabetes throughout the world.

The United Nations General Assembly passed a resolution last December which recognizes diabetes as a chronic, debilitating and costly disease. It designated World Diabetes Day as a United Nations Day to be observed every year starting in 2007. The theme of this year’s campaign is Diabetes in Children and Adolescents.

My Parent/Sibling has Type 1 Diabetes – Will I?

This is a common question asked of physicians in their clinical encounters. It is very difficult to answer in most diseases unless there are certain proven facts that have been standardized with clinical trials and reports.

Type 1 diabetes is characterized by:

• Its genetic inheretance
• Complete dependency on insulin treatment
• Young age onset
• Autoimmune destruction of beta cells in pancreas (Body defense cells called lymphocytes destroy own body cells)
• Development of ketoacidosis

Role of Autoimmunity :

Lymphocytes target beta cells in pancreas and destroy them slowly. So in time there will be no insulin in the body and diabetes will develop. What triggers this self-destruction is not quite known but any external viral or toxic factor alters beta cells and makes them foreign to lymphocytes. So lymphocytes think that those are not the body’s own cells and destroys them.

Supporting this autoimmune theory there are anitibodies detected in the person’s blood against beta cells, lymphocytes found in the pancreas causing insulitis and this type 1 autoimmunity is associated with other autoimmune diseases.

Role of Genetic Inheritance :

Type 1 diabetes has a complex pattern of inheritance with susceptibility genes mapped to at least 20 loci. The most important is the class II HLA locus. Certain HLAs are strongly associated with diabetes type 1. Roughly 95% of all type 1 diabetics have HLA-DR3, HLA-DR4 or both. HLA-DQ genes are even more specific markers for type 1 diabetes (HLA-DQB1*302).

Family members of a diabetic are at increased risk for developing type 1 diabetes. A child has a 3% risk of developing diabetes if its mother is a type 1 diabetic. That percentage doubles to 6% should it be the father with type 1 diabetes.

The risk between siblings is based on the number of haplotypes shared between them. If one haplotype is shared the risk is 6% and with two haplotypes the risk is increased to 25%. The risk for identical twins is 25 – 50%.

Role of Environmental factors :

There are many viral infections are thought to be triggering factors for the development of autoimmunity. Examples are coxsackie virus type B, mumps, measles, cytomegalovirus, rubella and infectious mononucleosis.

All these are not thought to be directly destroying the beta cells. But one propsed theory is that when a virus infects pancreatic cells, the resulting cell damage causes the release of beta cell antigens. Lymphocytes exposed to these antigens get sensitized and then destroy beta cells.

Another proposed theory is viral cells produce antigens that mimic beta cell antigens so lymphocytes sensitized to these viral antigens destroy beta cells in addition to the viral cells.

The three factors described are accurate in classic type 1 diabetes for 90% of all cases. But in less than 10% of cases no reason will be found. And these type 1 diabetics are included under the ’Idiopathic’ group. Recently it was reported that a mutation in the gene that is essential for the development of pancreatic islets is involved in this particular group of patients.

Diabetes – Effects on Kidneys

Diabetes – Effects on kidneys. (Diabetic nephropathy)

Advanced kidney disease is seen 30 – 40% of type 1 diabetics and 20 – 30% of type 2 diabetics.

What causes glomerulosclerosis?

• Metabolic defects – like insulin deficiency, hyperglycemia are responsible for alterations in glomerular basement membrane causing its thickening.
• Advanced glycosylation end products – AGEs have effects like altering endothelial, mesangial and macrophage cellular functions, modifying LDL cholesterol so it oxidized and deposited within vessel walls causing atheromas, generation of reactive oxygen species.
• Hemodynamic changes – Early stages of diabetes, there is increased glomerular capillary pressure and glomerular hypertrophy with slowly developing glomerulosclerosis.
• Cytokines like TGF-beta causes hypertrophy of the mesangial cells and deposition of the collagen in the glomerulus.

Lesions in kidney :

Glomerulus:

Basement membrane thickening – BM of the glomeruli becomes thick. This can be diagnosed electron microscopy.

Cells in between the glomeruli (mesangial cells) increase in number and deposition of pink substance leading to mesangial thickening.

Glomerular lesions – Called Kimmelstiel Wilson disease. Consists of ball like deposits at the periphery of the glomerulus. These contain mesangial cells and PAS postive substance and surrounded by patent capillary loops. As disease advances whole glomerulus become sclerosed.

Arteriosclerosis:

Renal afferent and efferent arterioles become thickened as a part of macrovascular disease.

Infections:

Pyelonephritis is infection of the kidneys. Both acute and chronic types can be seen. These are also seen in general population, but more common in diabetics.

How diabetic kidney manifests in clinical practice?

Microalbuminuria – Urinary excretion of 30 – 300 mg per day of albumin. Slowly frank nephrotic syndrome develops. Diagnosed by overnight collection of urine. This can be done 3 times in 3 – 6 months period. Two of three values are abnormal, then it is said that patient has microalbuminuria.

Frank nephrotic syndrome – develops overtime with hypoalbuminemia, edema, increased circulating cholesterol. As renal failure progresses, glucose appears in urine. Protein will be more than 3.5 g/d. There will be rising blooad urea nitrogen and creatinine ratio.

Management of nephropathy includes -

Strict control of glucose has been shown that intensive therapy can partially reverse glomerular hypertrophy and hyperfiltration, delay the development of microalbuminuria.

Angiotensin converting enzyme inhibitors – Decrease progress of diabetic glomerulopathy. Also decreases mean arterial pressure and microalbuminuria. Usually combined with diuretics in long term.

In end stage disease dialysis and renal transplantation are considered.

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