Diabetes mellitus Overview Types Causes,Symptoms with Diagnosis
Diabetes mellitus is a group of metabolic disorders with hyperglycemia.
Glucose intolerance is characterized by hyperglycemia resulting from defects in glucose and fat metabolism. Overt diabetes is classified as type 1 (T1DM), type 2 (T2DM), and gestational (GDM) A chronic metabolic disorder marked by hyperglycemia. Diabetes mellitus (DM) results either from failure of the pancreas to produce insulin (type 1 DM) or from insulin resistance, with inadequate insulin secretion to sustain normal metabolism (type 2 DM).
Hyper glycemia is due to :
- · Decreased insulin secretion
- · Decreased glucose usage
- · Increased production of glucose.
- Hyperglycemia and associated metabolic disturbances causes involvement of multiple organ systems leading to morbidity and mortality.
Diabetes mellitus is of two types according to etiology:
TYPE I DIABETES:
- Type 1: There is absolute insulin deficiency or defective insulin secretion.
- There is pancreatic Beta cell destruction leading to absolute insulin deficiency.
- Type I occurs usually at less than 30 years age.
- Type I A diabetes –
- Immune mediatedAuto immune beta cell destruction leading to insulin deficiency.
- Type I B diabetes
- Idiopathic insulin deficiency Tendency to ketosis
- – No immunologic marker
- – Cause unknown
- Common in Asians.
TYPE 2 DIABETES
- There is insulin resistance, insulin deficiency, and defect of insulin secretion.
- Type 2 is
- · Due to insulin resistance
- · Impaired insulin secretion
- · Increased glucose production
- · There is genetic and metabolic defect leading to hyperglycemia.
Two terms: Insulin dependent diabetes mellitus (IDDM or type 1) and Non Insulin dependent diabetes mellitus (NIDDM or type 2) are now not used as NIDDM may also require insulin later in life. In obese adolescents type 2 diabetes mellitus may be seen.
- A. Genetically defined, monogenic form of DM MODY-maturity onset diabetes of the young
- · 5 different variants of MODY
- · Mutation in genes encoding islet transcriptase factors
- · Autosomal dominant disorders
- · Homozygous mutation causes severe neonatal diabetes.
- Genetic defects of beta cells due to mutations- Maturity onset diabetes of the young called MODY is a subtype of diabetes mellitus which is autosomal dominant, early onset hyperglycemia, with impaired insulin secretion.
- • MODY I – MODY 6
- B. Genetic defect in the action of insulin.
- · Type A – Insulin resistance
- · Leprechaunismb
- · Rabson-Mendenhall syndrome
- · Lipodystrophy.
- C. Diseases of pancreas
- D. Endocrinopathies
- · Acromegaly
- · Cushing’s syndrome
- · Pheochromocytoma
- · Hyperthyroidism
- · Glucagonoma.
- E. Drug induced
- · Thyroid hormones
- · Beta agonists
- · Thiazides
- · Phenytoin
- · Beta blockers.
- F. Infections
- G. Anti-insulin receptor antibodies
- H. Genetic syndromes
- · Down’s syndromes
- · Klinefelter’s syndrome
- · Turner’s syndrome
- · Friedreich’s ataxia
- · Myotonic dystrophy
- · Huntington’s chorea.
IV. GESTATIONAL DIABETES MELLITUS
- Occurs in pregnant females due to insulin resistance related to metabolic changes in later pregnancy.
- Reverts to normal usually. Seen in 4% of pregnancies.
- May develop into diabetes mellitus later in life 60%).
- Characteristics of the onset of disease (e.g., DKA, routine lab evaluation)
- Diet and exercise history
History of diabetes-related complications:
- Microvascular: Eye, kidney, nerve
- Macrovascular: Cardiac, cardiovascular disease, peripheral artery disease
- Other: Sexual dysfunction, gastroparesis
- Tobacco and alcohol use
- Unexplained weight loss (sometimes accompanied by polyphagia)
- Blurred vision
- Blood pressure, including orthostatics
- Dorsalis pedis and posterior tibialis pulses
- Funduscopic exam
- Thyroid palpation
- Skin exam (for acanthosis nigricans and insulin injection sites), trophic changes on toes
- Neurological exam:
- ›Patellar and achilles reflexes
- ›Proprioception, vibration, and monofilament sensation tests
Normal glucose tolerance
- FPG (Fasting plasma glucose) mg/dl normal tolerance ( <110) impaired fasting glucose tolerance (110-125) —
- 2hPG (2h plasma glucose) (glutose load 75g)
- RBG (Random)
- Normal glucose tolerance test
- FPG – Fasting plasma glucose (no calorie intake in past 8 hrs).
- RBG (Random) any time irrespective of last meal (~ 200 mg/dl in DM).
- HbA1c as a diagnosis test for diabetes mellitus is not standardized.
- Categorized as IFG when diagnosed using a fasting plasma glucose (FPG) or IGT when diagnosed using the oral glucose tolerance test (OGTT):
- IFG: FPG 100 mg/dL and <126 mg/dL
- IGT: A 2-hour plasma glucose between 140 mg/dL and 199 mg/dL following ingestion of a 75-g glucose load
- Diagnosed using any one of the following 3 tests, each of which must be confirmed on a subsequent day. A1C should not be used to diagnose diabetes
- FPG: Preferred test, FPG 126 mg/dL
- Casual plasma glucose (CPG) and symptoms of diabetes. CPG is measured at any time of day, regardless of time since last meal. CPG 200 mg/dL accompanied by
- Criteria for Diagnosis of Diabetes Mellitus
For screening of diabetes mellitus
symptoms is diagnostic
- OGTT: More sensitive and specific than FPG, but poorly reproducible; not recommended for routine clinical use. A 2-hour plasma glucose 200 mg/dL following ingestion of a 75-g glucose load is diagnostic
- Type 2 – FPG is done because patient may have type 2 diabetes mellitus for 10 yrs before being diagnosed.
- 50% of patients of type – 2 diabetes mellitus have one or more complications at the time of diagnosis.
- Type I diabetes mellitus is usually symptomatic from the onset itself.
- Type I diabetes mellitus there are immunological markers.
- The likelihood of type 2 diabetes mellitus is more in the following:
- · Family history of diabetes (parents and sibling with type 2 diabetes mellitus)
- · Obesity ~ 20% desired body weight
- Age> 45 yrs
- Race – Asian, Africans
- Impaired fasting glucose (IFG) or Impaired glucose tolerance (IGT)
- H/o gestational diabetes mellitus or baby’s weight more than 9 pounds
- BP > 140/90 mmHg
- HDL < 35 mg/dl or TG > 250 mg/dl Polycystic ovarian syndome (POD).
- Insulin is produced by beta cells of pancreas. Glucose levels of less than 70 mg/dl stimulate synthesis of insulin.
- Meals and other stimuli cause release of insulin in bursts every 10 minutes or so and lasting upto 3 hours.
- Impaired fasting glucose or Diabetes Mellitus Impaired glucose tolerance
- Type 1 A diabetes mellitus – Pancreatic beta cells are destroyed due to genetic, environmental and immunologic factors.
- The destructive process is progressive.
- When 80% beta cells are destroyed overt diabetes appears.
- When there is increased insulin requirement as during puberty or infection overt diabetes occurs.
- There is a honeymoon period when without insulin blood sugar is controlled due to reduced insulin requirement. Gradually all the beta cells are destroyed by autoimmune process and there is complete .insulin deficiency leading to diabetes.
- Type 1 A diabetes mellitus involves multiple genes.
- Type 1 A – concordance in twins is 30 – 70%.
- Most have HLA DR3 or DR4 haplotype.
- But most persons with HLA DR-3 or DR-4 do not have diabetes.
- Most with type lA diabetes mellitus do have a first degree relative with this disorder.
- B. In type 2 diabetes mellitus there is strong genetic component. Disease is polygenic and multifactorial.
- Insulitis – Pancreatic islets are infiltrated with Iymphocytes.
- Islet cells antibodies are present in majority of individuals (more than 75%) with new onset type 1 A diabetes mellitus, in a minority of individuals with type 2 diabetesmellitus and occasionally (5%) in individuals with gestational diabetes mellitus.
Environmental factors –
- Viruses-Coxsackie and Rubella, and bovine milk intake (proteins) may cause type 1 A.
- Prevention of type I
- · By administration of insulin to induce immune tolerance
- · Immunosuppression
- · Selective T cell subset deletion
- · Induction of tolerance to islet proteins
- · Blocking cytotoxic cytokines
- · Increase islet resistance.