Diabetes Mellitus It’s Types, Lab Findings, and Treatment

Diabetes mellitus is a clinical syndrome characterized by hyperglycemia due to the absolute or relative deficiency of insulin. Long-standing metabolic derangement can lead to the development of complications of diabetes, which characteristically affect the eyes, kidneys, and nervous system. Diabetes occurs worldwide, and its prevalence is rising; 366 million people had diabetes in 2011, and this is expected to reach 522 million by 2030. Diabetes is a significant burden upon health care facilities across the world.

Diabetes mellitus is classified into the following categories: type 1, type 2, and gestational diabetes mellitus. 

Type 1 diabetes usually begins during childhood and results from autoimmune destruction of pancreatic B cells.

Type 2 diabetes is a progressive disorder characterized by increasing insulin resistance and diminishing insulin secretory capacity. 

Latent autoimmune diabetes in adulthood (LADA) is a mild autoimmune form found in 10–15% of type 2 diabetes patients. Type 2 diabetes is frequently associated with obesity and is much more common than type 1 diabetes. Although type 2 diabetes usually begins in adulthood, the cases in children and adolescents are rising dramatically, parallel with the increase in obesity in the population.

Type 1 Diabetes (Insulin Dependent)

Type 1 diabetes is invariably associated with profound insulin deficiency requiring replacement therapy. It is a T cell-mediated autoimmune disease leading to progressive destruction of the insulin-secreting B cells. Classic symptoms occur only when 80-90% of B cells have been destroyed. Pathology shows insulitis infiltration of islets with mononuclear cells, in which Beta cells are destroyed, but cell secreting glucagon and other hormones remain intact. Islet cell antibodies can be detected before clinical diabetes; however, they are not suitable for screening diagnostic purposes. 

Type 1 is a severe form associated with ketosis in the untreated state. It occurs commonly in juveniles but occasionally in adults, especially the non-obese and elderly, when hyperglycemia first appears. It is a catabolic disorder in which circulating insulin is virtually absent, plasma glucagon is elevated, and the pancreatic B cells fail to respond to all insulinogenic stimuli. Exogenous insulin is therefore required to reverse the catabolic state, prevent ketosis, and reduce hyperglucagonemia and the elevated blood glucose level.

Type 1 diabetes is thought to result from infectious or toxic environmental insult in people whose immune system is genetically predisposed to develop a vigorous autoimmune response against pancreatic B cell antigens. 

Genetic Predisposition

Genetic factors account for about one-third of the susceptibility to type 1 diabetes, with 35% concordance between monozygotic twins.

Environmental Factors

Environmental factors play an essential role in type 1 diabetes. Viral infections implicated in the etiology include mumps, coxsackie B4, retroviruses, and congenital rubella. Various nitrosamines found in smoked and cured meats and coffee have been proposed as potentially diabetogenic toxins.

Type 2 Diabetes (Insulin Independent)

Type 2 diabetes is characterized by tissue resistance to the action of insulin combined with a relative deficiency in insulin secretion. An individual may have more resistance or beta-cell lack, and the abnormalities may be mild or severe. Although insulin is produced by the beta cells in these patients, it is inadequate to overcome the resistance, and the blood glucose rises. The impaired insulin action also affects fat metabolism, resulting in increased free fatty acid flux and triglyceride levels and reciprocally low-density lipoprotein (HDL).

Dehydration in individuals with untreated or poorly controlled type 2 diabetes can lead to a life-threatening condition called a nonketotic hyperosmolar coma. In this condition, the blood glucose may rise to 6–20 times the normal range, and an altered mental state develops,s or the person loses consciousness. Urgent medical care and rehydration are required. 

Type 2 diabetes also represents a heterogeneous group comprising milder forms of diabetes that occurs predominantly in adults, but occasionally, in adolescents. Circulating endogenous insulin is sufficient to prevent ketoacidosis but is often subnormal or relatively inadequate because of tissue insensitivity. Obesity, which generally results in impaired insulin action, is a common risk factor for diabetes. And most patients with diabetes type 2 are obese. In addition to tissue insensitivity to insulin, which has been noted in most type 2 patients irrespective of weight, there is an accompanying deficiency of the pancreatic B cells’ response to glucose.

Genetic Factors

Genetic factors are important in type 2 diabetes; different ethnic groups have different susceptibility, but monozygotic twins have concordance rates approaching 100%; however, many genes are involved. 

Other Risk Factors

Type 2 diabetes is mainly associated with overeating, especially when combined with obesity and under activity. The risk of developing type 2 diabetes increases tenfold in people with body mass index BMI greater than 30 Kg/m. however, a minority of obese people develop diabetes.

Gestational Diabetes

Glucose metabolism changes during pregnancy. Marked insulin resistance develops, particularly by the second half of pregnancy, due to maternal hormones such as human placental lactogen. Fasting glucose decreases slightly, while blood glucose may be increased post-prandially.

Gestational diabetes is defined with the first onset or recognition during pregnancy. While this includes a few who develop type 1 and type 2 diabetes during pregnancy, most can expect to return to standard glucose tolerance immediately after pregnancy. The definition of diabetes in pregnancy is based on maternal glucose levels associated with increased fetal growth and is lower than non-gestational diabetes.

Signs and Symptoms of Diabetes Mellitus

Type of Test for Normal Pre-Diabetes

Fasting

• Glucose test – less than 100 
• 100-125
• 126 or higher

Random (anytime)

• Glucose test – less than 140
• 140-199
• 200 or higher

A1c Test Less than 5.7%

• 5.7 – 6.4%
• 6.5% or higher

Insulin

Insulin is a small protein molecule within the B cells insulin precursor produced by DNA or RNA directed synthesis.

Insulin is produced from pancreatic B cells at a low basal rate and a much higher stimulated rate in response to various stimuli.

The kidney and liver are the two most important organs that play a crucial role in maintaining the insulin level in the body, presumably by hydrolysis of the disulfide connection between the A and B chains.

Treatment with Insulin

The current classification of diabetes mellitus identifies a group of patients who have virtually no insulin secretion and whose survival is dependent on the administration of exogenous insulin (Type 1 diabetes).

Most type 2 diabetics are insulin-independent, which means they do not require insulin for survival. Still, at the same time, many need nutritional supplements to achieve the optimum level of health. 

Insulin Secretagogues

•  Rapid-acting: Lispro, Aspart, glulisine
•  Short-acting: Regular
•  Intermediate-acting: NPH
•  Long-acting: Detemir, glargine

Insulin delivery systems

1.Portable pen injectors

2.Continuous subcutaneous insulin infusions 

3.Inhaled insulin 

Oral Anti-diabetic Agents 

Seven categories of oral anti-diabetic agents are now available for the treatment of persons with type 2 diabetes:

1) Sulfonylureas, meglitinides, D-phenylalanine derivatives)

• Sulfonylureas 
• Glipizide 
• Glyburide
• Glimepiride, 

2) Biguanides, 

• Metformin

3) Thiazolidinediones,

•  Rosiglitazone 
•  Pioglitazone

4) α-glucosidase inhibitors, 

• Acarbose,
• Miglitol

5) Incretin-based therapies, an amylin analog, 

• Pramlintide

6) Bile acid binding sequestrant. 

• Colesevelam 
• Hydrochloride

The sulfonylureas and biguanides are accessible the longest and are the ordinary treatment decision for type 2 diabetes. Novel classes of fast-acting insulin secretagogues, the meglitinides, and D-phenylalanine subordinates, are options compared to the short-acting sulfonylureas. Insulin secretagogues increase insulin discharge from beta cells. Biguanides decline hepatic glucose creation. The thiazolidinediones lessen insulin obstruction. The incretin-based treatments control post-food glucose losses by expanding insulin discharge and diminishing glucagon on emission.

The amylin simple additionally diminishes post-dinner glucose levels and decreases craving. Alpha-glucosidase inhibitors moderate the assimilation and ingestion of starch and disaccharides. Albeit still theoretical, the instrument of bile corrosive sequestrant’s glucose-bringing assumed impact down to be identified with a lessening in hepatic glucose yield.

 Treatment with Herbal Remedies

• Chromium

• Zinc

• Aloe Vera

• Cinnamon

• Ginger

Management of Diabetes.

Of new cases of diabetes, approximately 50% can be controlled adequately by diet alone, 20-30% will need oral anti-diabetic medication, and 20-30% will require insulin.

Regardless of etiology, the choice of treatment is determined by the adequacy of residual B cell function. However, this cannot be determined easily by the measurement of plasma insulin concentration. A level that is adequate in one patient may be inadequate in another, depending on sensitivity to insulin. Ideal management allows the patient to lead an utterly everyday life, to remain symptom-free, and to escape the long-term complication of diabetes. The correct treatment may change with time as B cell function is lost. 

• Diet and Lifestyle 

Lifestyle changes, such as taking regular exercise, observing a healthy diet, reducing alcohol consumption, and stopping smoking, are significant but difficult for many to sustain. 

• Healthy Eating

Dietary measures are required in the treatment of all people with diabetes. People with diabetes should have access to dietitians at diagnosis, at review, and at times of treatment change. Nutritional advice should be tailored to the individual and take account of their age and lifestyle. The aims are to improve glycaemic control, manage weight, and avoid both acute and long-term complications. 

• Carbohydrate

The effect of particular ingested carbohydrate on blood glucose is relative to the effect of glucose drinks termed the glycaemic index. Starchy foods, such as rice, porridge, and noodles, are favored, as they have a lower glycaemic index and produce only a gradual rise in blood glucose. 

• Fat 

Eating an excessive amount of fat can cause you to take in additional calories than your body needs, which causes weight gain, which may affect your diabetes control and overall health.

• Salt

For diabetes management, it’s essential to limit the use of salt because too much consumption of salt can raise your blood pressure.

• Weight management

Many people with type 2 diabetes are overweight or obese, and many anti-diabetic medications and insulin encourage weight gain. Abnormal obesity also predicts insulin resistance and cardiovascular risk. Weight loss is achieved by reducing energy intake and an increase in energy expenditure through physical exercise.

• Exercise

All patients with diabetes should be advised to achieve a significant level of physical activity like walking, gardening, swimming, cycling, or playing soccer and to maintain this long term. Supervised exercise programs may be of particular benefit to people with type 2 diabetes. 

• Alcohol  

Alcohol can be consumed in moderation. Aas alcohol suppresses gluconeogenesis; it can precipitate or prolong hypoglycemia, particularly in patients taking insulin or sulphonylureas.

Long Term Supervision of Diabetes

Diabetes is a complex disorder that progresses in severity with time. Patients with diabetes should, therefore, be seen at regular intervals throughout their lives and possibly include neuropathy therapies. The frequency of visits varies from weekly during pregnancy to annually in well-controlled type 2 diabetes.

Complications of Diabetes 

•  Diabetic Retinopathy
•  Diabetic Nephropathy
•  Diabetic Neuropathy
•  Alzheimer’s disease
•  Cardiovascular disease

Reference

Davidson’s Essentials of Medicines

Bonus video: Diagnosing diabetes | Endocrine system diseases

Diabetes Mellitus It’s Types, Lab Findings, and Treatment

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