Diabetes Mellitus – Inheritance Pattern and Global Statistics

Diabetes Mellitus –  A Comprehensive View of Inheritance Pattern and Global Statistics
Dr.Mansi Arya
Email : dr.mansiarya333@gmail.com

Diabetes mellitus is one of the most common endocrine disorders affecting almost 6% of the world’s population. The number of diabetic patients will reach 300 million in 2025 (International Diabetes Federation, 2001).

Global Burden of Disease
The prevalence of diabetes for all age-groups worldwide was estimated to be 2.8% in 2000 and 4.4% in 2030. The total number of people with diabetes is projected to rise from 171 million in 2000 to 366 million in 2030. The greatest relative increases will occur in India , the Middle Eastern Crescent and sub-Saharan Africa .The greatest absolute increase in the number of people with diabetes will be in India. The 10 countries estimated to have the highest numbers of people with diabetes in 2000 and 2030 are listed in Table 3. The “top three” countries are the same as those identified for 1995 (India, China, and U.S.).

Ranking Countries People with Diabetes (in millions) in 2000 People with Diabetes(in millions) in 2030

Statistics from WHO Global Burden of Disease project , carried out by WHO and Harvard University for the World Bank. …

The projected increase in the number of diabetic patients will strain the capabilities of healthcare providers the world over. Thus it is of paramount importance to revisit the causes and epidemiology of diabetes mellitus.

Causes
Insufficient production of insulin (either absolutely or relative to the body’s needs), production of defective insulin (which is uncommon), or the inability of cells to use insulin properly and efficiently leads to hyperglycemia and diabetes.

Type 1 diabetes is believed to be an autoimmune disease. The absolute lack of insulin, usually secondary to a destructive process affecting the insulin producing beta cells in the pancreas, is the main disorder in type 1 diabetes.
A predisposition to develop type 1 diabetes may run in families but much less so than for type 2.
Environmental factors, such as certain types of viral infections, may also contribute.
Type 1 diabetes is most common in people of non-Hispanic white persons of Northern European descent, followed by African Americans and Hispanic Americans. It is relatively rare in those of Asian descent.
Type 1 diabetes is slightly more common in men than in women.

Type 2 diabetes: The primary problem is the inability of cells to use insulin properly and efficiently mostly affecting the cells of muscle and fat tissues results in a condition known as “insulin resistance.”. There also is a steady decline of beta cells that adds to the process of elevated blood sugar. Initially production of insulin increases to overcome the level of resistance. But gradually production declines and insulin cannot be released as vigorously resulting in hyperglycemia
Type 2 diabetes has multifactorial or polygenic pattern of inheritance , that means it is likely associated with the effects of multiple genes in combination with lifestyle and environmental factors .Thus believed to have a strong genetic link, it tends to run in families. Several genes are being studied that may be related to the cause of type 2 diabetes.

Risk factors for developing type 2 diabetes include the following:-

• High blood pressure
• High blood levels of cholesterol and/or triglyceride
• Gestational diabetes or giving birth to a baby weighing more than 9 pounds
• High alcohol intake
• Sedentary lifestyle
• Obesity
• Positive Family History
• Ethnicity: Certain groups, such as African Americans, Native Americans, Hispanic Americans, and Japanese Americans, have a greater risk of developing type 2 diabetes than non-Hispanic whites.
• Aging: Increasing age is a significant risk factor for type 2 diabetes. Risk begins to rise significantly at about age 45 years, and rises considerably after age 65 years.

Diagnostic Criteria
1. Fasting Plasma Glucose Level
Plasma Glucose (mg/dL) Diagnosis
99 and below Normal
100 to 125 Pre-diabetes
(impaired fasting glucose)
126 and above Diabetes*

2. Post Prandial (2 hr)Glucose Level
Plasma Glucose (mg/dL) Diagnosis
139 and below Normal
140 to 199 Pre-diabetes
(impaired glucose tolerance)
200 and above Diabetes*
*Confirmed by repeating the test on a different day.

3. Gestational Diabetes: Above-Normal
Results for the Oral Glucose Tolerance Test
When Plasma Glucose Result (mg/dL)
Fasting 95 or higher
At 1 hour 180 or higher
At 2 hours 155 or higher
At 3 hours 140 or higher

Management and Treatment
Maintenance of blood sugar is essential to feeling healthy and avoiding long-term complications of diabetes. Some people are able to control their blood sugar with diet and exercise alone. Others may need to use insulin or other medications in addition to lifestyle changes. In either case, monitoring of blood sugar is a key part of your treatment program.

1. Monitoring Your Blood Sugar-
As the amount of sugar in blood is constantly changing. Self-monitoring helps one cognizant to what makes blood sugar levels rise and fall, so that one adjustments could be made accordingly
The best range for patient depends on his age . For younger adults who don’t have complications of diabetes, a typical target range might be 80 to 120 mg/dL fasting , and below 180 mg/dL PP. Older adults who have complications from their disease may have a fasting target goal of 100 to 140 mg/dL and below 200 mg/dL PP. If patient is on insulin, blood sugar should be checked atleast twice a day. Glycated hemoglobin or HbA1c is also used to monitor treatment in patients with diabetes mellitus;

2. A Healthy Diet
The diabetic diet should consist of carbohydrates, fats and proteins. Half of the calories should come from complex carbohydrates. This comprises, whole grain breads, cereals, fruit, vegetables and low fat milk. a diabetic diet is all about calories, the right sort of carbohydrates in the right form, salads and vegetables, low fat yogurt, skimmed milk, fruit (preferably an apple, orange or a mosambi), and cereals with low glycemic index. Polysaturated or monosaturated fats help increase HDL cholesterol, and reduce LDL cholesterol. Corn oil, safflower and soybean oil are good mediums.A low fat diet , adequate protein and low salt intake should complete it. Rounded off with adequate exercise, you should have the diabetes under control.

VITAMIN and MINERAL THERAPY
Vitamin E.
People with diabetes have a higher than usual need for vitamin E, which improves insulin activity and acts as an antioxidant and a blood oxygenator. A vitamin E deficiency results in increased free-radical-induced damage, particularly of the lining of the vascular system. Supplemental vitamin E may help prevent diabetic complications through its antioxidant activity, the inhibition of the platelet-releasing reaction and platelet aggregation, increasing HDL-cholesterol levels and its role in fatty acid metabolism.
Good sources of Vitamin E include wheat germ, sunflower seeds, pine nuts, sun-dried tomatoes and almonds.

Vitamin C
People with Type 1 diabetes (IDDM) have low vitamin C levels. Vitamin C lowers sorbitol in diabetics. Sorbitol is a sugar that can accumulate and damage the eyes, nerves, and kidneys of diabetics. Vitamin C may improve glucose tolerance in Type 2 diabetes (NIDDM).
The transport of vitamin C into cells is facilitated by insulin. It has been postulated that, due to impaired transport or dietary insufficiency, a relative vitamin C deficiency exists in the diabetic and that this may be responsible for the increased capillary permeability and other vascular disturbances seen in diabetics.
If you are diabetic, supplement your diet with 1-3 grams per day of vitamin C.

Vitamin B6 (Pyridoxine)
Diabetics with neuropathy have been shown to be deficient in vitamin B6 and benefit from supplementation. Peripheral neuropathy is a known result of pyridoxine deficiency and is indistinguishable from diabetic neuropathy. Vitamin B6 supplements improve glucose tolerance in women with diabetes caused by pregnancy. Vitamin B6 is also effective for glucose intolerance induced by the birth control pill. 1,800 mg per day of a special form of vitamin B6-pyridoxine alpha-ketoglutarate-improves glucose tolerance dramatically.
Pyridoxine is also important in preventing other diabetic complications because it is an important coenzyme in the cross-linking of collagen and inhibits platelet aggregation.

Vitamin B12
Vitamin B12 supplementation has been used with some success in treating diabetic neuropathy. It is not clear if this is due to the correcting of a deficiency state or normalizing vitamin B12 metabolism.
Vitamin B12 is needed for normal functioning of nerve cells. Vitamin B12 taken orally, intravenously, or by injection reduces nerve damage caused by diabetes in most people.

Biotin
Biotin is a B vitamin needed to process glucose. It has been shown to work synergistically with insulin and independently in increasing the activity of glucokinase. This enzyme is responsible for the first step in glucose utilization. Glucokinase is present only in the liver, where, in diabetics, its concentration is very low.

Niacin
High levels-several grams per day-of niacin, a form of vitamin B3, impair glucose tolerance . So, avoid it if you are diabetic. Smaller amounts (500-750 mg per day for one month followed by 250 mg per day) of niacin may help some people with Type 2 diabetes (NIDDM).

Chromium
As a key constituent of the ‘glucose tolerance factor,’ chromium is a critical nutrient in diabetes. Supplementation in the form of chromium chloride (200 micro g daily) or high-chromium-containing brewer’s yeast (9 g a day) has been demonstrated to decrease fasting glucose levels, improve glucose tolerance, lower insulin levels and decrease total cholesterol and triglyceride levels, while increasing HDL-cholesterol levels.

Manganese
Manganese is an important cofactor in the key enzymes of glucose metabolism. A deficiency of manganese was found to result in diabetes in guinea pigs. It also resulted in the frequent birth of offspring who develop pancreatic abnormalities or no pancreas at all. Diabetics have been shown to have only one-half the manganese of normal individuals.

Magnesium
Magnesium levels are significantly lowered in diabetics, and lowest in those with severe retinopathy. Studies suggest that a deficiency in magnesium may worsen the blood sugar control in Type 2 diabetes. Scientists believe that a deficiency of magnesium interrupts insulin secretion in the pancreas and increases insulin resistance in the body’s tissues. Studies suggest that a deficiency in magnesium may worsen the blood sugar control in Type 2 diabetes. Scientists believe that a deficiency of magnesium interrupts insulin secretion in the pancreas and increases insulin resistance in the body’s tissues.

Potassium
Potassium supplementation yields improved insulin sensitivity, responsiveness and secretion in diabetics. Insulin administration often causes a potassium deficiency.

Zinc
Zinc deficiency has been suggested to play a role in the development of diabetes in humans. Zinc is involved in virtually all aspects of insulin metabolism -synthesis, secretion and utilization.

Carnitine
Carnitine is a substance needed for the body to properly use fat for energy. When diabetics are given carnitine (1 mg per 2.2 pounds of body weight), high blood levels of fats-both cholesterol and triglycerides-dropped 25-39% in just ten days. In addition, carnitine improves the breakdown of fatty acids, possibly playing a role in preventing diabetic ketoacidosis

Taurine
Taurine is an amino acid found in protein-rich food. People with Type 1 diabetes (IDDM) have low taurine levels, that leads to “thickened” blood-a condition which increases the risk of heart disease. Supplementing taurine (1.5 grams per day) restores taurine levels to normal and corrects the problem of blood viscosity within three months.

3. PHYSICAL ACTIVITIES
Everyone needs regular aerobic exercise, and people with diabetes are no exception.
Walking, hiking, jogging, biking, tennis, cross-country skiing and swimming are all good choices.Aim for at least 30 minutes of aerobic exercise most days
* Exercise helps reduce blood glucose levels and makes insulin more effective.
Exercise also helps people lose weight faster.
Exercise helps people maintain their lower weight.
Exercise is believed to improve insulin’s sensitivity (its ability to work).
Exercise reduces the dosage requirement or the need for blood-glucose medications
Exercise reduces the risk of cardiovascular disease.

4. HEALTHY WEIGHT
Being overweight is the greatest risk factor for type 2 diabetes. That’s because fat makes your cells more resistant to insulin. But when you lose weight, the process reverses and your cells become more receptive to insulin. For some people with type 2 diabetes, weight loss is all that’s needed to restore blood sugar to normal. Furthermore, a modest weight loss of 10 to 20 pounds is often enough.

5. MEDICATIONS
Medications used to treat diabetes include insulin. Everyone with type 1 diabetes and some people with type 2 diabetes must take insulin every day to replace what their pancreas is unable to produce.

A number of drug options exist for treating type 2 diabetes, including:
Sulfonylurea drugs. These medications stimulate your pancreas to produce and release more insulin. For them to be effective, your pancreas must produce some insulin on its own. Second-generation sulfonylureas such as glipizide (Glucotrol, Glucotrol XL), glyburide (DiaBeta, Glynase PresTab, Micronase) and glimepiride (Amaryl) are prescribed most often. The most common side effect of sulfonylureas is low blood sugar, especially during the first four months of therapy. You’re at much greater risk of low blood sugar if you have impaired liver or kidney function.
Meglitinides. These medications, such as repaglinide (Prandin), have effects similar to sulfonylureas, but you’re not as likely to develop low blood sugar. Meglitinides work quickly, and the results fade rapidly.
Biguanides. Metformin (Glucophage, Glucophage XR) is the only drug in this class available in the United States. It works by inhibiting the production and release of glucose from your liver, which means you need less insulin to transport blood sugar into your cells. One advantage of metformin is that is tends to cause less weight gain than do other diabetes medications. Possible side effects include a metallic taste in your mouth, loss of appetite, nausea or vomiting, abdominal bloating, or pain, gas and diarrhea. These effects usually decrease over time and are less likely to occur if you take the medication with food.

Alpha-glucosidase inhibitors. These drugs block the action of enzymes in your digestive tract that break down carbohydrates. That means sugar is absorbed into your bloodstream more slowly, which helps prevent the rapid rise in blood sugar that usually occurs right after a meal. Drugs in this class include acarbose (Precose) and miglitol (Glyset). Although safe and effective, alpha-glucosidase inhibitors can cause abdominal bloating, gas and diarrhea. If taken in high doses, they may also cause reversible liver damage.
Thiazolidinediones. These drugs make your body tissues more sensitive to insulin and keep your liver from overproducing glucose. Side effects of thiazolidinediones, such as rosiglitazone (Avandia) and pioglitazone hydrochloride (Actos), include swelling, weight gain and fatigue. A far more serious potential side effect is liver damage.

Homoeopathic Treatment
Diabetes mellitus being a chronic disease is treated effectively by homoeopathic medicines.
1.Constitutional medicine-based on the constitution of the patient the most indicated medicine covering all the symptoms is prescribed. Some useful constitutional medicines found are Lycopodium, Sulphur, Argentum nitricum, Natrum mur, Calcarea carb.
2.Palliative medicines-These have an physiological effect on reducing blood sugar. Some well indicated medicines are Syzigium jambolanum, Gymnema, Cephalendra indica, Insulim .

Research
A study was made to determine the place of homeopathy in the treatment of D.M. (Scope and limitation of homeopathy in diabetes mellitus Möglichkeiten und Grenzen der Homöopathie bei Diabetes mellitus SK Patra1 Diabetes Research Centre, Bhubaneswar, India).
During this study, the diabetic subjects were divided into two groups- one on only diet and exercise and the other on diet and exercise and homeopathic simmilum(remedy). it was seen than ¾ of the patients responded to homeopathic medicines. The constitutional medicines selected on the basis of the totality of symptoms collected after proper case taking are effective for D.M. Some mother tinctures, Insulin 3X and Sea buckthorn (Leh-berry) have shown efficacy in controlling the D.M. in different stages.

Genetic analysis of late-onset type 2 diabetes in a mouse model of human complex trait.
Ueda H, Ikegami H, Kawaguchi Y, Fujisawa T, Yamato E, Shibata M, Ogihara T. Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan.
Type 2 diabetes is a complex trait with both genes and environmental factors contributing to susceptibility.

Except for rare subtypes with monogenic inheritance, the genetic basis of type 2 diabetes is unknown because of the complex and heterogeneous nature of the disease. By using the NSY mouse, an inbred mouse model of type 2 diabetes, we genetically dissected late-onset type 2 diabetes and demonstrated age-dependent changes in the genetic control of type 2 diabetes as well as polygenic inheritance. Three major loci (Nidd1nsy, Nidd2nsy, Nidd3nsy) were mapped on mouse chromosomes (Chr) 11, 14, and 6, respectively. The existence of a fourth locus (Nidd4nsy) with an age-dependent effect was suggested by longitudinal, but not cross-sectional, analysis of linkage data. Nidd1nsy and Nidd4nsy appear to affect insulin secretion, whereas Nidd2nsy and Nidd3nsy appear to affect insulin sensitivity. A locus on Chr 6 was significantly linked to epididymal fat weight. A candidate disease gene (Tcf2) on Chr 11, encoding hepatic nuclear factor-1beta, was shown to have a rare sequence variant in the DNA binding domain in the model. The mouse model we used will serve as a useful model for future studies on the etiology of late-onset polygenic type 2 diabetes in humans.

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