Bioenergy Conservation and Diabetes mellitus

Diabetes mellitus (DM) is related to common metabolic disorders and is expressed by hyperglycemia (i.e. elevated level of glucose in blood). There are a variety of DM and are caused by complex interactions of genetics and environmental factors. In fact DM is a sort of lifestyle associated metabolic disorder. Sedentary lifestyle, over indulgence in alcohol and excessive consumption of fatty fast-food laced with preservatives are the cause of excessive conservation of bioenergy in human body. One should be calorie conscious and take balanced diet to avoid getting obese and over weight. Obesity is an invitation to metabolic disorders.
Non-insulin dependent diabetes mellitus (NIDDM) is also known as diabetes-II (or Type-II Diabetes, where as Diabetes-I is insulin dependant) and is characterized by variable degree of insulin resistance and pancreatic beta cell dysfunction. Loss of metabolic control is probably associated with neuroendocrine control system that effect hepatic glucose output. Computerization and automation in industrial units is the cause of bioenergy conservation in workers, leading to metabolic disorders like diabetes mellitus. Low energy expenditure due to leisure-way lifestyle and reduced sensitivity to peripheral insulin further complicate the case. Vascular complications associated with DM lead to morbidity and mortality in patients with diabetes mellitus. Energy expenditure needs to be increased in diabetics by way of exercise; brisk walking and cycling.  Optimum energy expenditure in diabetics can act as adjunct to reduce the level of hyperglycemia.

Itching and Associated Diseases

Itching or pruritus is defined as the skin sensation that prompts the patient to scratch a particular area of the skin. Irritative stimulation of skin is caused due to activation of free nerve endings situated at the dermo-epidermal junction. Itching is a physiologic or pathologic symptom caused due to internal or external factors. Itch receptors present in the free nerve endings at the dermo-epidermal junction are stimulated by histamine and other anaphylactic substances and evoke motor response of scratching. If not controlled, scratching may lead to skin injury and infection. There is a scratching itch cycle and one feels relieved after the itching cycle. Itching or pruritus is the most common disease of the skin caused by innumerable causes. If the cause of itching/pruritus remains undiagnosed even after two weeks then it is labeled as pruritus of undetermined origin (PUO). The cause of itching/pruritus could be local or systemic. It can be associated with the following systemic diseases.

Renal disease and pruritus:

Chronic renal failure (CRF) is a well-recognized cause of generalized and persistent pruritus. Uremia during CRF and cellular changes in the skin could be the possible cause of itching/pruritus. It is not directly related to renal function parameters, as patients with acute renal failure (ARF) do not complain of itching.

Liver disease and pruritus:

Patients with liver disease may also present with mild transient or severe or persistent sensation of itching. Intra-hepatic or extra-hepatic cholestasis in these patients leads to pruritus or itching. Primary billiary cirrhosis, cholangitis, viral infections, drugs and pregnancy can cause intra-hepatic cholestasis and lead pruritus.

Pregnancy and pruritus:

Pregnant women with mild abnormalities of liver function in the form of cholestasis may develop itching in the third trimester of pregnancy. Three out of 100 pregnant women may have pruritus.

Endocrine diseases and pruritus:

Pruritus confined to genital or peri-anal areas is most common in diabetics. Patients with diabetes mellitus sometimes may present with pruritus as the main presenting feature for medical consultation. Patients suffering from hypothyroidism and hyperthyroidism may also have generalized itching or pruritus.

Pruritus in occult malignancies:

Intense itching of nostrils has been observed in patients with tumors of brain. Adenocarcinomas and squamous cell carcinomas of various organs may also lead to generalized itching/pruritus. Around 30% patients with Hodgkin's disease have been found to be affected by itching disorder; some patients may show these symptoms as presenting features.

Type-2 Diabetes and the role of incretins

The incretins are the hormones, which are released into the blood circulation in response to nutrients we eat. These peptide hormones are generally released within minutes of eating or enteral nutrition. In humans, the major incretins are: (i) Glucagon like peptide-1 (GLP-1) and (ii) Glucose-dependent insulinotropic polypeptide (GIP). GLP-1 is secreted by L-cells in the ileum and colon, while GIP is secreted by K-cells in the duodenum of our alimentary canal. GLP-1 and GIP stimulate insulin secretion by the pancreas and also affect the gut and the brain. Their combine effect make significant contribution in glucose homoeostasis, particularly in scaling down the peak of postprandial glucose level. It has been proved through experimental studies that the GLP-1 has the major incretin effect; that is around 80% of the combine effect of GLP-1 and GIP. These incretins probably act via glycoprotein-coupled receptors.

Non-insulin dependent diabetes mellitus (NIDDM) or type-2 diabetes mellitus (Type-2 DM) is characterized by pancreatic beta-cell dysfunction and variable degree of insulin response. Complex interaction of genetics and environmental factors are responsible for metabolic disorders leading to diabetes. Taming of hyperglycemia through medicines, dietary control and regular exercise is possible. Increasing prevalence of obesity and reduced physical activity is directly related to the increasing prevalence of type-2 DM, worldwide. Oral antidiabetic agents, diet and or exercise and insulin are currently used for the treatment of patients with diabetes. Existing antihyperglycemic agents are often associated with an increased risk of adverse effects (such as weight gain and hypoglycemia) and most often become less effective due to histological/cellular variations (progressive beta cell failure) in the pancreas of the patient.

Incretins provide insulinotropic stimulus and thus lower the blood glucose level by increasing insulin secretion. However, the incretin response to a meal lasts approximately around 3 hours as the incretin molecules have very short half-life (<5 minutes) and are metabolized quickly. An enzyme known as dipeptidyl peptidase-4 (DPP4), produced by endothelial cells, disintegrate the incretin molecules within 2-3 minutes of their secretion. Poor incretin response has been observed in patients with type-2 diabetes during the glucose tolerance test as indicated by reduced level of GLP-1 as compared to normal individuals. The functional response (insulinotropic response) of GLP-1 was found to be intact in patients with type-2 diabetes and that gave new direction to the treatment regimen of diabetes. At present the incretin system has been under active study to find out the effective compounds for the treatment of type-2 diabetes. Pharmaceutical compounds like: (1) GLP-1 'analogues' or GLP-1 receptor agonists which are resistant to breakdown by DPP4 and (2) Incretin enhancers which inhibit the action of DPP4 on GLP-1 molecules, have been under active study for use in new formulations.

Exenatide is already in clinical use after its approval by US-FDA. Exenatide is a biosynthetic form of GLP-1 analogue-exendin-4. Exendin-4 is a naturally occurring GLP-1 found in the saliva of a lizard known as Gila monster. It was approved by US-FDA in 2005 for use in combination with metformin or sulfonylureas or both together. Exenatide is administered twice daily before meals by subcutaneous injections from a pre-filled pen. Incretin enhancers improve the control of glucose level in blood by inhibiting DPP4 action on incretin hormones especially GLP-1 molecules. Incretin enhancer Sitagliptin was approved by US-FDA in 2006 and Vildagliptin was approved by US-FDA in 2007, and both have been used as monotherapy or in combination with antidiabetic drugs like metformin or thiazolidinedione for glycemic control in patients affected by type-2 diabetes.

Important Note: Antihyperglycemic treatment should always be taken in consultation with a physician or specialized diabetologist.

Diabetes and Pregnancy

Pregnancy brings a sea change in the metabolism in pregnant women. Your bodyhas to produce extra insulin to meet the requirements of your body during pregnancy, especially from 4^th month onwards. Hormonal changes during pregnancy may interfere with the insulin function and if your body can't cope with the situation, you may develop gestational diabetes. Women with family history of diabetes mellitus, older mothers and obese women are at the risk of developing gestation diabetes mellitus (GDM). The diabetes mellitus in pregnancy could be classified as pre-gestational or gestation diabetes mellitus. One out of fourteen cases of pregnancy may develop GDM in second or third trimester of pregnancy due to effect of placental hormones. Ideally, all pregnant women should be tested to rule out gestation diabetes. The routine examination of urine for sugar, on every visit to the gynaecologist could give an indication about onset of gestation diabetes and need for further investigations and medication. If elevated level of blood sugar is observed on random blood sugar (RBS)investigation, one should go for glucose tolerance test (GTT). Diabetic mothers need extra care to prevent spontaneous abortion and malformations in infants. Babies born to diabetic women, who were diabetic before they became pregnant, would have a greater risk of health problems, if diabetes was poorly controlled. Babies grow bigger in diabetic expectants due to extra sugar crossing the placenta and may make labour and delivery more difficult. Periodic screening, dietary control and proper medication are must to avoid GDM associated complications in expectant mothers and babies born.

How can we prevent Diabetes?

High blood glucose level may also be detected in non-diabetics after major meals. In most of us, even when our blood glucose level skyrockets after a carbohydrate rich meal, our body tames it down in 2-3 hours. Only in diabetics, blood glucose levels persist quite high for most of the time. It is possible to prevent diabetes for ever if we plan the calorie content of our diet. Low glycemic-index (GI) meals with low carbohydrate content should be preferred as compared to fast acting high-GI carbohydrates. Green leafy vegetable, citrus fruits, soybeans, kidney beans, green peas, pistachio, peanuts and walnuts are some low-GI food stuffs you can include in your diet. The bread and chapaties made from wholegrain flour do have low-GI. Fruits and vegetable are also packed with vitamins, minerals and fibre. Fruits and vegetables are beneficial to keep the blood glucose levels within the limits of renal threshold. Protein rich meals have low-GI, help to curb hunger and prevent diabetes. Vegetarians may include legumes, nuts, peanut butter and milk to their diet whereas non-vegetarians may take lean meat, fish and poultry products. Acidic foods have been known to tame blood glucose level. Salad and pickles seasoned with vinegar should be taken with major meals for sustainable metabolism with respect to blood glucose level and prevention of diabetes.

All Diabetics are not Alike!

All diabetics are not alike, so never take medicines for diabetes on the advice of fellow patients. The term diabetes means inordinate and persistent excretion of excessive volume of urine. Diabetes is a disease of carbohydrate metabolism with a variety of causes. Pancreas is directly associated with carbohydrate metabolism and biobalance of blood sugar (glucose) level. All carbohydrates (starches, polysaccharides, disaccharides and monosaccharides) are converted into glucose in our stomach and small intestine, absorbed in blood and taken to liver for storage in liver cells as glycogen for future use. Glycogen is also stored into muscle cells and utilized for muscle function. Insulin produced by the beta-cells in the pancreas helps in the penetration of glucose into liver and muscle cells and further storage as glycogen. Glucagon produced by alpha-cells of the pancreas regulates the conversion of glycogen in glucose through glycogenolysis, when ever glucose level in the blood falls below normal.

Defective metabolism of carbohydrates may lead to alimentary diabetes. The term diabetes insipidus pertains to a condition characterized by excessive intake of water with excessive urination but without any glycosuria (excretion of glucose in urine). Diabetes insipidus due to congenital failure of renal tubules to respond to anti-diuretic hormone (ADH) is termed as diabetes insipidus nephrogenic. Diabetes mellitus (DM) is a condition characterized by an elevated level of sugar (glucose) in blood and urine. Diabetes mellitus may affect both younger (juvenile diabetes) and older people (maturity onset diabetes). Subclinical diabetes refers to a condition where glucose tolerance test is abnormal but clinical signs of diabetes like polyuria (excessive urination with increased frequency of micturition), hunger, thirst and weight loss are absent. Obesity may be associated with diabetes but all obese people could never be diabetics. Fat metabolism is also impaired in diabetes which may lead to hypercholesterolemia and hypertension (high blood pressure) in diabetics. There is a strict need of controlling hypertension and hypercholesterolemia with customized diet, regular exercise and sometimes with medicines. It is advisable never to copy your fellow patient's treatment. Diabetes need your round the clock commitment and if taken care it would reduce your risk of serious complications like renal disease.

Important Tip: Never copy your fellow patient's treatment.