Diabetes Mellitus:- Part 2 – Diabetes Mellitus, Diagnosis and Management

Diabetes Mellitus

What Sample for Glucose Estimation is needed?

1. This test can be done on Serum. The Serum should be separated within 30 minutes of collection.
2. The Serum can be stored at 25 °C for 8 hours and at 4 °C for 72 hours.
3. Oxalated blood can also be used. Preservative sodium fluoride may be added.
4. The plasma can be stored at 25 °C for 24 hours (with preservative sodium fluoride).

How much is the Stability of the sample for glucose?

1. One milliliter of blood in an anticoagulant containing fluoride will remain stable for 3 hours.
2. Oxalate plasma is stable at 2 to 8 °C for 48 hours.
3. Mostly Serum is used, stable for 8 hours at 25 °C and 72 hours at 4 °C.
4. A 6 to 8-hour fast is required for a fasting sample.

What are the indications for Diabetes Mellitus Patients?

1. This test is done to diagnose diabetes mellitus.
2. This test is also done to evaluate and monitor the patient with Diabetes mellitus.

What Screening indications for Diabetes are advised in individuals?

1. People aged 45 or older are assessed at 3-year intervals.
2. Younger individuals should be screened if they are obese (>120% of the desired weight) or have a body mass index ≥ 27.
3. Individuals with H/O first-degree relatives with Diabetes.
4. In the case of high-risk ethnic groups, African Americans, Hispanic Americans,  Native Americans, and Asian Americans.
5. Babies delivered weighing>9 lbs, and there is a previous H/O GDM (gestational diabetes mellitus).
6. Individuals with hypertension ≥140/90 mm Hg and H/O atherogenic dyslipidemia.
   1. HDH-Cholesterol = ≤35 mg/dL.
   2. Triglycerides         = ≥250 mg/dL.

How will you Define Diabetes mellitus?

1. Diabetes mellitus is a group of metabolic disorders characterized by impaired carbohydrate metabolism, leading to hyperglycemia.
2. This is not a single disease but a group of disorders, and glucose intolerance is common among them.
3. Diabetes mellitus describes a syndrome characterized by chronic hyperglycemia and disturbances of carbohydrate, protein, and fat metabolism.
4. Diabetes Mellitus is a metabolic disorder characterized by hyperglycemia that results from defects in insulin secretion, insulin action, or both.
   1. This condition is also associated with abnormalities in protein and fat metabolism.
   2. Diagnosis is dependent upon hyperglycemia and glucosuria.

Diabetes mellitus and insulin action

What are the Complications of diabetes mellitus?

1. Chronic hyperglycemia leads to:
   1. Changes in the retina and lens of the eye (retinopathy)
   2. Damage to the kidneys.
   3. Microalbuminuria.
   4. Nephropathy
   5. The heart, arterial system, and microcirculation are adversely affected.
   6. Increased risk of heart disease problems.
   7. These patients may develop neuropathy.
   8. The foot needs care and may develop gangrene.
   9. These patients may develop hearing problems.
   10. There is a chance of Alzheimer’s disease.

Diabetes Mellitus

What are the Criteria for the Diagnosis of Diabetes Mellitus?

1. Polyuria, polydipsia, and rapid weight loss.
2. Fasting glucose level is high.
3. Insulinopenia occurs when insulin secretion is reduced due to β-cell loss in the pancreas.
4. Most patients have an autoantibody, which is an autoimmune process.
5. When no cause is known, it is called idiopathic Type.
6. Abnormal Glucose tolerance test.

What are the types of Diabetes  Mellitus (classification of diabetes mellitus)?

1. Type 1 diabetes mellitus (Insulin-dependent, IDDM).
   1. There is β-cell destruction, usually leading to absolute insulin deficiency.
   2. This may be immune-mediated.
   3. It may be Idiopathic.
2. Type 2 diabetes mellitus (Noninsulin-dependent, NIDDM).
   1. There is predominantly insulin resistance with relative insulin deficiency. OR
   2. There may be predominantly an insulin secretion deficiency with insulin resistance.
3. Gestational Diabetes Mellitus (Gestational diabetes mellitus, GDM).
   1. It is detected early in pregnancy. This may be type 1 or type 2.
   2. This is detected in the 2nd or 3rd trimester in 4% of pregnant women.
4. Other specific types are:
   1. The genetic defects of β-cell dysfunction.
   2. The genetic defect in insulin action (Type A insulin resistance).

What are the causes of diabetes mellitus?

1. Diseases of the pancreas (exocrine glands).
   1. Pancreatitis.
   2. Trauma or pancreatectomy.
   3. Tumor of the pancreas.
2. Drugs or chemicals induced.
   1. Thiazide.
   2. Glucocorticoids.
   3. Nicotinic acid.
3. Infections.
   1. Cytomegalovirus (CMV).
   2. Congenital rubella.
4. Endocrinopathies.
   1. Glucagonoma.
   2. Cushing’s syndrome.
   3. Acromegaly.
5. Immune-mediated diabetes.
6. Genetic syndromes associated with diabetes mellitus are:
   1. Turner syndrome.
   2. Down’s syndrome.
   3. Myotonic dystrophy.
   4. Friedreichs Ataxie.

Diabetes Mellitus Type 1 (Insulin-dependent diabetes mellitus, IDDM)

How will you define Type 1 Diabetes Mellitus?

1. This is also called:
   1. Juvenile-onset Diabetes.
   2. Juvenile Diabetes.
   3. Ketosis-prone diabetes.
   4. Brittle Diabetes.
   5. Autoimmune Diabetes.
   6. Idiopathic Diabetes.
2. There is a long preclinical period, followed by an abrupt onset of clinical manifestations.
3. Patients are prone to developing ketoacidosis.
4. There is a dependency on insulin.
5. This often affects young people around puberty.
   1. The peak age of onset is 11 to 13 years.
   2. The risk for the sibling is 5% to 10%, while the risk for the offspring is 2% to 5%.
6. There are several syndromes of autoimmune and genetic origin.

What is the pathogenesis of type 1 diabetes mellitus?

1. The autoimmune phenomenon may be the cause of  type 1 diabetes mellitus:
2. Type 1 diabetes mellitus is due to cell-mediated autoimmunity that leads to the destruction of pancreatic β-cells.
   1. The islet cells are infiltrated by mononuclear cells, a condition called insulitis.
   2. The autoimmune process for type 1 diabetes begins years before the clinical presentation.
   3. An 80% to 90% reduction in the volume of β-cells is needed before clinical Diabetes appears.
   4. Destruction of the β-cells is more rapid in children than in adults.
3. While other α, δ, and other islet cells are preserved.

The pancreas produces insulin

4. Antibodies that may play a role in type 1 diabetes are:
   1. There is a marker of β-cell autoimmunity in which antibodies in the serum are detected before Diabetes appears.
   2. Islet cell cytoplasmic antibodies.
   3. Insulin auto-antibodies.
   4. Glutamic acid decarboxylase antibodies.
5. Genetic  role:
   1. Type 1 diabetes is inherited, but the mode of inheritance remains unclear.
6. Environmental factors:
   1. There are various factors reported, and one of those is the virus.
   2. Viruses such as mumps, Bella, and coxsackievirus B are blamed.
   3. Other factors like cow’s milk and chemicals.
7. This is because of the severe or complete absence of insulin due to the loss of beta cells in the pancreas.
8. Destruction of the islet cells may be due to the following:
   1. Genetics.
   2. Autoimmunity.
   3. Environmental factors.
9. In 80% to 90% of cases, islet cell autoantibodies and antibodies to insulin and glutamic acid decarboxylase cause damage to the islet cells.
10. Non-immune type 1 diabetes can occur secondary to other diseases, such as pancreatitis.
11. Pathology: Beta-cell abnormalities are present long before the onset of type 1 diabetes mellitus.
    1. Both beta and alpha cell functions are abnormal, with a lack of insulin and a relative excess of glucagon produced by the alpha cells.

What are the signs and symptoms of diabetes mellitus Type 1?

1. Glucose accumulates in the blood (hyperglycemia)  and is excreted in the urine.
2. Weight loss occurs due to the breakdown of proteins and fats.
3. There is polyuria, polyphagia, and polydipsia.
4. There is a wide fluctuation in the blood glucose level.
5. There may be ketoacidosis because of the breakdown of protein and fat.
   1. There are increased ketone bodies.
6. The pH drops, triggering the buffer system and leading to metabolic acidosis.
   1. 1. There is a fruity odor in the breath due to the volatile ketone body acetone.
7. The patient may go into a coma.

What are the clinical manifestation and their explanation?

What is the Treatment of Diabetes Mellitus Type 1?

1. This will need a combination of the following:
   1. Insulin.
   2. Food planning.
   3. Exercise.
   4. More details are discussed at the end of this discussion.

Diabetes Mellitus Type 2 (NON-Insulin dependent NIDDM)

How will you define Diabetes mellitus type 2?

1. This is also called:
   1. Adult-onset type diabetes.
   2. Maturity-onset Diabetes.
   3. Ketosis-resistant diabetes.
2. Patients have minimal symptoms.
3. This is not dependent on insulin to prevent ketonuria.
4. The insulin level may be normal, decreased, or increased.
5. Most patients have impaired insulin action.
6. There is the interaction of metabolic, genetic, and environmental factors.
7. It affects people after the age of 40 years, and mostly these people are obese.

How will you discuss the pathophysiology of diabetes mellitus type 2?

1. The cause is unknown.
2. Genetics may play some role, but it is not clearly defined.
3. There is no evidence of the autoimmune mechanism.
4. Cellular resistance is a factor in 60% to 80% of people with type 11 diabetes mellitus.
5. Insulin resistance increases with obesity.
6.  There is a decreased response of the β-cell to blood glucose levels and abnormal glucagon secretion.
7. There may be alterations in the insulin-receptor or post-receptor events.
   1. There may be an increase in insulin levels to compensate for insulin resistance in peripheral tissues, but there is still relative insulin deficiency.
8. The changes in the pancreas are nonspecific:
   1. 10% to 40% of the cases show amyloidosis of the pancreas in type 2 diabetes mellitus.
   2. Pancreatic fibrosis occurs in 33% to 66% of cases with type 2 diabetes, leading to a decreased number of β-cells.
   3. Generally, there is a decrease in the weight and number of β-cells, and the cause is unclear.
9. The most common factor is obesity. It increases 10 times in obese people.
10. Also, excessive intake of calories predisposes to type 2 diabetes.
11. Insulin can not facilitate the entry of glucose into the muscle cells, hepatocytes, and fat cells.
12. One factor is decreased insulin action on peripheral tissues (insulin resistance).

What are the signs and symptoms of diabetes mellitus type 2?

1. These are nonspecific.
2. Most patients are obese and overweight.
3. There is hyperlipidemia.
4. Onset is slow and mostly not noted, which leads to late diagnosis.
5. Classic symptoms like polydipsia, polyphagia, and polyuria are present.
6. There may be nonspecific symptoms like pruritus, recurrent infections, paresthesia, and visual changes.

What is the Treatment of Diabetes Mellitus Type 2?

1. This is just like type 1 diabetes.  The aim is to keep blood sugar in the normal range.
2. There is a need to decrease the calorie intake in an overweight person.
3. Saturated fats and cholesterol are restricted.
4. Some people recommend a high-fiber diet.
5. Oral hypoglycemic drugs may be needed.
6. Exercise also helps.
7. Insulin may also be given.

What factors will affect glucose level?

1. Stress, such as trauma, general anesthesia, infection, burns, and Myocardial infarction, can increase the glucose level.
2. Caffeine may increase the level.
3. Some pregnant women may experience glucose intolerance. A significantly elevated glucose level is called Gestational Diabetes.
4. Drugs may increase the glucose level, such as an antidepressant (tricyclic), Beta-blockers, corticosteroids, I/V glucose, dextrothyroxine, diazoxide, diuretics, estrogen, glucagon, isoniazid, lithium, phenothiazine, phenytoin, and salicylates.
5. Drugs like acetaminophen, alcohol, anabolic steroids, insulin, tolbutamide, propranolol, and clofibrate may decrease the glucose level.

What are the American diabetes association recommendations?

What are the Clinical manifestations and their explanation in Diabetes mellitus?

Gestational diabetes mellitus

How will you define Gestational diabetes mellitus?

1. Definition: Hyperglycemia develops for the first time during pregnancy.
2. This is also called:
   1. Asymptomatic Diabetes.
   2. Chemical Diabetes.
   3. Borderline Diabetes.
   4. Latent Diabetes.
   5. Subclinical Diabetes.
3. Gestational diabetes mellitus develops when glucose intolerance develops during pregnancy, so all pregnant women need to be tested.
4. After delivery, glucose levels return to normal, remain impaired, or progress to Diabetes.
5. This is first diagnosed during pregnancy and usually in the third trimester.
6. Already known cases of diabetic women are not included in this group.
7. This occurs in 6% to 8% of pregnant women (another source, only 2% of pregnant women may have this Diabetes).
8. Out of this group, 60% may develop Diabetes in 15 years of gestation.
9. Later on, these ladies are at increased risk of developing diabetes mellitus (6% to 62% of these ladies).

What are the risk factors for gestational diabetes?

1. Risk factors in developing Gestational Diabetes are:
   1. Pregnant ladies with Glycosuria.
   2. If there is a family history of Diabetes.
   3. In obese ladies.
   4. If the ladies develop pregnancy at a late age.
   5. In multiparity of 5 or more.
   6. In the case of previous complicated pregnancies.

What are the diagnostic criteria for gestational diabetes mellitus?

1. To diagnose gestational diabetes mellitus.
2. Two blood samples on oral glucose tolerance tests (with 100 grams of glucose) are as follows:

Gestational diabetes mellitus (GDM)

What is the Treatment of gestational diabetes mellitus?

1. Advise random or fasting blood glucose during pregnancy.
2. It should be aggressive to prevent morbidity and fetal mortality.

Impaired glucose tolerance (IGT)

How will you define impaired glucose tolerance?

1. This group has less fasting glucose than required for diabetes mellitus.
2. An oral glucose tolerance test is needed to diagnose this group.
3. The overt case develops at a rate of 1% to 5% per year.
   1. 10% to 20% will convert to type 11 diabetes within 10 years.
4. Microvascular diseases are very uncommon in this group.
5. Many of them are obese.

What are the Criteria for impaired glucose tolerance?

1. With an oral glucose tolerance test:
   1. 2-hour sample = ≥140 mg/dL.
   2. Nonpregnant ladies = <200 mg/dL.

Impaired fasting glucose (IFG)

How will you define impaired fasting glucose?

1. There is an abnormal response to an oral glucose tolerance test.

What are the Criteria for the diagnosis of Impaired fasting glucose?

1. Fasting glucose = ≥110 mg/dL and <126 mg/dL.
2. 2 hours of glucose = ≥ 140 mg/dL.
   1. 1. 1. 1. =<200 mg/dL.
3. This is diagnosed by fasting glucose values between normal and diabetic individuals.
4. This is a metabolic stage between normal glucose and diabetes mellitus.
5. There is an increased risk for the development of Diabetes and cardiovascular disease.

What are the Latest classification criteria for Diabetes mellitus?

1. Diabetes mellitus:
   1. Presence of classic symptoms.
   2. If the fasting glucose level is 126 mg/dL (>7.0 mmol/L) or higher, it should be labeled as Diabetes Mellitus (when this value is found twice).
   3. One random glucose level>than 200 mg/dL (11.1 mmol/L) with symptoms of polyuria, polydipsia, and polyphagia is considered diagnostic of Diabetes.
   4. HbA1c =>6.5 is diagnostic of Diabetes.
   5. The 2-hour postprandial glucose level was≥200 mg/dl  (11.1 mmol/L) during OGTT.
2. Impaired fasting glucose = >126 mg/dl. (fasting glucose level 110 to 125 mg/dL (6.1 to 7.0 mmol/L).
3. Impaired glucose tolerance when:
   1. Fasting glucose <126 mg/dl (7 mmol/L).
   2. OGTT 2-hour sample is 140-199 mg/dL (7.8-11.1 mmol/L).

What are the Criteria for the diagnosis of diabetes mellitus?

1. Fasting blood glucose level:
   1. 126 mg/dL (7.0 mmol/L) or higher is considered diagnostic.
2. Random/nonfasting blood glucose level:
   1. 200 mg/dL (11.1 mmol/L) is diagnostic.
3. Oral glucose tolerance test with 75 G of glucose:
   1. A 2-hour sample of 200 mg/dL  (11.1 mmol/L) or higher value is diagnostic.

What are the Values in diabetic patients and normal people?

What are the Differences between Diabetes Mellitus type 1 and type 2?

What is the normal fasting glucose level?

Source 1

•  To convert to SI units x 0.0555 = mmol/L
• Values vary from the biochemical method used.

Source 6 for glucose level

Source Tietz

Plasma/ serum glucose level

• Adult = 74 to 106 mg/dL (4.5 to 5.9 mmol/L)
• Children = 60 to 100 mg/dL (3.5 to 5.6 mmol/L)
• Premature neonates = 20 to 60 mg/dL (1.1 to 3.3 mmol/L)
• Term neonates = 30 to 60 mg/dL (1.7 to 3.3 mmol/L)

The whole blood glucose level

• 65 to 95 mg/dL (3.5 to 5.3 mmol/L)

CSF glucose level

• 40 to 70 mg/dL (2.2 to 3.9 mmol/L)
  • 60% of the plasma

Urine 24-hour glucose level

• 1 to 15 mg/dL (0.1 to 0.8 mmol/L)

The normal value of glucose from another source:

1. Usually, glucose between 70 to 110 mg/dl is considered normal.
2. Fasting glucose = < 100 mg/dl.
   1. Cord blood = 45 to 96 mg/dL  (2.5 to 5.3 mmol/L)
   2. premature baby = 20 to 60 mg/dL.  (1.1 to 3.3 mmol/L).
   3. Neonates = 30 to 60 mg/dL  (1.7 to 3.3 mmol/L).
3. Infants = 40 to 90 mg/dL  (2.2 to 5.0 mmol/L).
4. Child <2 years = 60 to 100 mg/dL  (3.3 to 5.5 mmol/L).
   1. Child >2 years = like adult level.
5. Adult fasting = 70 to 110 mg/dL  (<6.1 mmol/L).
6. Adult random = <160 mg/dL  (11.1 mmol/L).

What are the various types of diabetes mellitus and glucose values?

Glucose curves in various conditions

Glucose values in whole blood, child/adult:

Diabetes Mellitus classification based on oral 75 G Glucose overload:

Critical values of Glucose:

What are the causes of raised glucose levels (Hyperglycemia)?

1. Diabetes mellitus, adult, and juvenile.
2. Physiological causes.
   1. Strenuous exercise.
   2. Strong emotions.
   3. Shock and burns.
   4. Infections.
3. Endocrine disorders.
   1. Thyrotoxicosis
   2. Acromegaly and gigantism.
   3. Pheochromocytoma.
   4. Cushing’s syndrome.
4. Pancreatic diseases.
   1. Acute and chronic pancreatitis.
   2. Pancreatitis due to mumps.
   3. Cystic fibrosis.
   4. Hemochromatosis.
   5. Pancreatic cancers.
5. Other causes are:
   1. Cerebrovascular accident.
   2. Chronic liver disease.
   3. Chronic renal disease.
   4. Acanthosis nigricans.

What are the causes of decreased glucose levels (Hypoglycemia)?

1. Pancreatic disorders.
   1. Islet Cell Tumor.
   2. Glucagon deficiency.
2. Tumors.
   1. Adrenal gland carcinoma.
   2. Carcinoma of the stomach.
   3. Fibrosarcoma.
3. Liver diseases.
   1. In poisoning, e.g., arsenic, chloroform, carbon tetrachloride, phosphorus, salicylates, antihistamines, phenformin, and alcohol.
4. Endocrine disorders.
   1. Hypopituitarism.
   2. Addison’s disease.
   3. Hypothyroidism.
5. Functional disorders.
   1. Postgastrectomy.
   2. Gastroenterostomy.
   3. Autonomic nervous system disorders.
6. Pediatric causes.
   1. Prematurity.
   2. Infant diabetic mothers.
   3. Idiopathic leucine sensitivity.
7. Enzyme deficiency.
   1. Galactosemia.
   2. Fructose intolerance.
   3. Von Gierke’s syndrome.

What are the complications of Diabetes Mellitus?

Acute complications are:

1. There may be hypoglycemia.
2. Patients with uncontrolled hyperglycemia of Type I may develop life-threatening complications like diabetic Ketoacidosis.
   1. Without treatment, the patient may become acidotic and dehydrated and lose consciousness.
3. Type II may develop hyperosmolar coma.

Chronic complications are:

1. Peripheral neuropathy.
2. Diabetic retinopathy and cataract formation.
3. Cardiovascular microangiopathy.
   1. Coronary atherosclerosis.
   2. Myocardial infarction is 3 to 5 times more common in diabetic patients.
   3. AMI is the leading cause of death in diabetes mellitus type 2.
4. Peripheral vascular diseases like ischemia of the lower extremities, erectile dysfunction, and intestinal ischemia.
   1. Gangrene of the foot.
5. Diabetic kidney disease (diabetic nephropathy) may lead to end-stage renal disease.
6. Chronic pyogenic skin infection.
   1. Candidal infection of the skin.
7. The bones and joints show contracture.

Diabetes Mellitus Complications

Diabetes Mellitus Complications

How will you monitor patients with diabetes mellitus?

1. In the newly diagnosed patient, check glucose frequently.
2. The best times are:
   1. Before meals.
   2. At bedtime.
3. The goal of therapy is:
   1. To maintain euglycemia.
   2. Avoid hypoglycemia.
   3. Prevent cardiovascular diseases.
   4. Prevent neurological complications.

How will you treat patients with diabetes mellitus?

1. It requires several modalities to treat diabetic patients:
2. Diet control:
   1. This includes dietary fiber.
   2. Eat low glycemic index foods, which will not raise blood glucose. This glycemic index is 55 or low, including vegetables, fruits, pasta, grainy bread, and legumes.
   3. High-glycemic-index foods have a glycemic index above 77. This will include potatoes, white bread, and white rice.
   4. The addition of protein and fats can lower the Glycemic index.
   5. Artificial sweeteners can be used in cooking and baking.
   6. Fructose is a natural sweetener and does not increase glucose levels.
3. Medications to lower hyperglycemia are:
   1. The first-generation sulphonylureas are tolbutamide, tolazamide, acetohexamide, and chlorpropamide.
   2. Second-generation sulphonylureas are glyburide, glipizide, gliclazide, and glimepiride.
   3. Repaglinide.
   4. Nateglinide.
4. Drugs that lower the glucose level by their action on the liver, muscle, and adipose tissue are:
   1. Metformin.
   2. Thiazolidinediones.
5. Medications that affect the absorption of glucose are:
   1. Acarbose.
   2. Miglitol.
6. Incretins are oral insulin stimulators:
   1. GLP-1 receptor antagonists.
   2. DPP-4 inhibitors.
   3. Sodium-glucose co-transporter two inhibitors.
7. Insulin has various preparations.
8. Transplant of the pancreatic tissue.

What are the hormones produced by the pancreas related to glucose metabolism?

Questions and answers: