Diabetes Mellitus

September 6, 2021


Overview

Diabetes Mellitus is a group of metabolic disorders characterized by chronic hyperglycemia due to impaired insulin secretion, variable degrees of peripheral insulin resistance, or both. Diabetes Mellitus is common and according to WHO approximately 415 million adults have diabetes worldwide. This is estimated to be 1 in 11 of the world’s adult population. Diabetes is usually irreversible but patients can live a reasonably normal life by controlling blood glucose levels through lifestyle modification, exercise, and medicines and minimizing long-term complications. There are 2 main types of diabetes — type 1 and type 2, which can be distinguished by a combination of features.

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Types of Diabetes

Type-1 Diabetes

Type-1 diabetes is a rare autoimmune disorder (less than 10 % of all diabetes cases). Patients are lean, younger (less than 40, average at around age 5-7 or at puberty), and are most common in Europe. Include autoimmune and idiopathic forms. Genetic susceptibility and viral factors play a role in causing autoimmune disorders against the beta cells of the pancreas. The destruction of Beta Cells over months or years usually leads to absolute insulin deficiency.

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The terms (juvenile or adult-onset) or the type of treatment (insulin-dependent or independent) are not used now because of the overlap in age groups and treatments, particularly the age of onset, duration of symptoms, and family history. Type-1 can occur at any age, while type-2 is increasingly being diagnosed in children.

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Type-2 Diabetes

This disorder is relatively common in all populations. More than 90% of adults with diabetes have type-2 diabetes. The disease may be present for years in a subclinical form before diagnosis, and the incidence increases markedly with age (greater than 50 years) and degree of obesity. Genetics play a role but there is no evidence of immune involvement. It may range from predominantly insulin resistance with relative insulin deficiency to a predominantly insulin secretory defect with insulin resistance. Insulin levels are often high, especially early in the disease, and may fall during the later course of the disease. Obesity and weight gain are important determinants of insulin resistance in type-2 diabetes.

Gestational Diabetes

Pregnancy causes insulin resistance in all women, but only a few develop diabetes called gestational diabetes. Increase glucose level is treated with diet and medicines and insulin if needed. Glucose levels come to normal in the majority after the delivery.

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Other specific forms of diabetes

Diabetes may be secondary to other conditions in a small proportion of cases. It may be precipitated by an underlying illness and may be associated with autoimmune disease or hyperlipidemia. Other causes are:

  • Genetic defects of beta-cell function,  e.g. maturity-onset diabetes of youth (MODY), Mitochondrial DNA mutations, Neonatal diabetes, Mutation in proinsulin or insulin conversion.
  • The genetic defect of insulin action: Insulin receptor mutations ( including type A insulin resistance, Leprechaunism, Rabson-Mendenhall syndrome) Acanthosis nigricans, lipodystrophies
  • Diseases of the pancreas (e.g. trauma, Cystic Fibrosis, Chronic pancreatitis, Tropical diabetes, Hemochromatosis, Pancreatectomy, and Neoplasia
  • Endocrinopathies e.g. Cushing’s syndrome, acromegaly, Hyperthyroidism, Somatostatinoma, Aldosteronoma, Pheochromocytoma, and Glucagonoma. Autoimmune polyglandular syndrome 1 and 2, others.

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  • Uncommon forms of immune-mediated diabetes: stiff-person syndrome, Anti- insulin receptor antibodies, others
  • Drug or chemicals: Vacor, pentamidine, Glucocorticoids, Thyroid hormone, Beta-adrenergic agonist, diazoxide, Phenytoin, Thiazide Diuretics, Protease Inhibitors, gamma interferon, and therapeutic doses of niacin. Clozapine, HIV treatment
  • Toxins e.g. the rodenticide pyriminyl
  • Infections: Congenital rubella, cytomegalovirus, Coxsackie
  • Associated with genetic syndromes e.g. Down Syndrome, Klinefelter’s Syndrome, Turner Syndrome, Myotonic Dystrophy, Friedreich’s Ataxia, Wolfram’s Syndrome, Huntington‘s Chorea, Lawrence-Moon-Biedl syndrome, Prader-Willi syndrome, others

Signs and Symptoms of Diabetes

  • Increased frequency of urine especially at night times
  • Increased thirst and a dry mouth
  • Increased hunger, especially a predilection for sweet food
  • Weight loss
  • Fatigue
  • Weakness
  • Mood changes and irritability
  • Difficulty in concentration
  • Headaches
  • Blurred vision
  • Frequent infections and poor wound healing
  • Numbness of hands and feet
  • Itchy dry skin

In early type-2 DM, symptoms may be more subtle and consist of fatigue, poor wound healing, and paresthesia. The lack of symptoms is the main reason for the delayed diagnosis of type-2 Diabetes Mellitus.

Type 2 diabetes ( T2D ) and pre-diabetes belong to a metabolic syndrome thought to be caused by resistance to insulin. Thus, people with T2D often have associated disorders including hypertension, Dyslipidemia, non-alcoholic fatty liver disease, and polycystic ovarian syndrome in women. This cluster has been termed insulin resistance syndrome or metabolic syndrome. And is much more common in obese people.

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Diagnostic Criteria

Diagnosis of diabetes is made by fasting plasma glucose level, Hb A1c, and sometimes by oral glucose tolerance test.

The concentration of glucose measured in plasma is 11% greater than that of whole blood as red blood cells contain relatively little glucose. Venous plasma values are usually the most reliable for diagnostic purposes.

Normally blood glucose is tightly regulated and maintained within a narrow range – even small deviations become important. In symptomatic patients, single elevated blood glucose, measured by a reliable method indicates diabetes. In patients, without symptoms or mildly symptomatic patients, the diagnosis is confirmed by another test. An oral glucose tolerance test is done for borderline cases only.

Diagnostic Criteria Fasting Plasma Glucose
(FPG) mg /dl
Oral Glucose Tolerance Test
(OGTT) mg /dl
HbA1c %
NormalLess than 100
or < 5.6mmol/L
Less than 140
or <7.8 mmol/L
Less than 5.7
Pre diabetes100-125
or (5.6-6.9) mmol/L
140-199
or (7.8-11.0) mmol/L
5.7-6.4
Diabetes126 or more
or ≥ 7mmol/L
200 or more
or ≥ 11.1 mol/L
6.5 or more

The pre-diabetics are at increased risk for developing type-2 diabetes and cardiovascular disease in the future. Diagnosis of type – 2 diabetes is made when type – 1 diabetes and other types of diabetes are ruled out.

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Risk Factors for Type 2 Diabetes

  • Overweight BMI 25kg/m2 or more
  • Age ≥ 45
  • First-degree relative with diabetes
  • Sedentary lifestyle
  • Race, ethnicity
  • Previously identified impaired glucose test
  • History of gestational diabetes or delivery of baby > 4 kg (9lb)
  • Hypertension
  • HDL cholesterol level ≤ 0.90 mmole/l (<35mg/dl) and/or triglycerides level ≥ 2.82 mmole/l (>250mg/dl)
  • Polycystic ovarian syndrome
  • Acanthosis nigricans
  • History of heart disease

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People ≥ age 45 and all adults with additional risk factors described above should be screened for DM with an  blood sugar fasting level, HbA1C, or a 75-g  oral glucose tolerance test at least once every 3 years and yearly if results show impaired fasting glucose levels.

Treatment

The aims are to improve symptoms, and to minimize the risks of long-term complications. Treatment plans for diabetes include changes in diet, exercise, and medicines that reduce glucose levels including, insulin, oral Antihyperglycemics, and other medicines to treat or prevent complications.

Education is the key to achieving and maintaining a healthy lifestyle and managing diabetes. Diabetic patients should be well aware of the causes, signs and symptoms, complications of diabetes, and self-monitoring of glucose. Insulin-treated patients should be taught how to monitor their own glucose levels using finger-stick glucometers. Immediate knowledge of blood glucose can be used to guide their insulin dosing and to manage exercise and illnesses.

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Insulin is mandatory for type -1 diabetic patients but type 2 diabetes can be managed with oral glucose-lowering medicines, insulin sensitizers, and secretagogues in addition to insulin.

Blood glucose targets vary according to the individual but in general, the pre-meal target is 90-130mg/dl and after meals less than 180 mg/dl.

In people with type-2 diabetes, treatment of co-existing hypertension and hyperlipidemia is usually required. The target for blood pressure usually is 130/80 mmHg. Statin is advised for every diabetic patient greater than 40 years of age irrespective of baseline cholesterol levels.

Target levels for total cholesterol are less than 150 mg/dl (or less than 4 mmole/l) and an LDL cholesterol of less than 75mg/dl (or 2 mmole/l).

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