Significance of involuntary weight loss and its causes.

Significance of involuntary weight loss and its causes.
Weight loss may be voluntary or involuntary. Voluntary weight loss occur due to dieting,exercise and starvation or decreased intake in older people. But the weight loss is involuntary particular attention cshould be given since it may be  an indicator of underlying serious disease.Weight loss can be identified from the hospital or general practice weight record.In some patients weight loss occur without  an underlying cause ,which is regained and stabilise  over time.

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New drugs that give hope to diabetic patients

Diabetes is a disease that can affect multiple system in the body. Since the prevalence of this disease in the community is very high and there is high chance to develop various complication if it is not controlled well lot of drug trial are going on this field. Newer drugs with different modes of action are tried to bring the blood sugar under control. Three such drugs are recently approved for treatment.

They are 

For people with type 2 diabetes drugs approved are 

1. Exenatide injection (Byetta)

2. Sitagliptin (Januvia)

3. Pramlintide acetate (Symlin)

For those with type 1 diabetes along with insulin Pramlintide acetate (Symlin) can be tried.

Why this drugs are useful in diabetes?

Insulin secretion from pancreas is stimulated by GLUCOSE. These newer drugs target the hormone incretin. Incretins potentiate this glucose stimulated insulin secretion from pancreas. As the insulin synthesizing and secreting action of GLP-1 is preserved in type 2 diabetic patients this has been developed as therapeutic agent for this disease. These are useful in treatment irrespective of the severity and duration of the disease. Diabetes is a chronic progressive disease sometime the agent that works for a period of time may become less effective and ,then we need to introduce new one.

Basic mechanism of action of these drugs.

Incretin are produced in the intestine in response to food intake. Incretin effect is mainly  mediated by two peptide hormones, they are glucose-dependent insulin releasing polypeptide(GIP), and glucagon-like peptide-1(GLP-1). Both GIP and GLP-1 are rapidly metabolized  into inactive metabolites by the action of  dipeptidyl-peptidase-IV (DPP-IV) enzyme. As the insulin synthesizing and secreting action of GLP-1 is preserved in type 2 diabetic  patients this has been developed as therapeutic agent. These are useful in treatment irrespective of the severity and duration of the disease. Thus the modulation of GLP-1 levels and GLP-1 activity by administration of the native hormone, its analogs, and mimetics or the agents that inhibit its degradation has become the chief focus of investigation for type 2 diabetes  treatment.

Advantage of this drugs in diabetes.

1. They enhance the insulin secretion.In addition to its effects on insulin secretion, GLP-1.

2. Stimulate the insulin synthesis.

3. Inhibit  the glucagon secretion ,glucagons increases the blood sugar.

4. Delays the  gastric emptying thus reduces the sugar. 

5. Reduction of food intake.

6. It has trophic effects on the pancreas. Stimulate betacell proliferation.

Drugs act on GLP1 receptor are

1. Exenatide injection (Byetta)

Indicated in those people with type 2 DM whose blood sugar fails to bring under control with oral drugs. They helps to control the blood sugar by mimicking the insulin action and slowing stomach emptying. Since the patient feel full faster and stop eating these agents will help to reduce weight. This is given as injection 2 times a day at mealtime. Special advantage of this drug is it help to reduce weight and wont produce hypoglycemia. But there is risk of hypoglycemia if taken with other agents that enhance the insulin secretion. Side effect of this drugs are nausea, inflammation of pancreas, risk of kidney disease. Exenatide should not be used in people with kidney disease. Approved for either as single therapeutic agent or in combination with other drugs. To minimize the initial side effect treatment started at lower doses, dose limiting side effect is nausea that is tendency to vomit. Exenatide extended release (Bydureon) advantage of this extended release formulations is it require injection only once a week. Action and side effects are similar to Byetta.

2. Liraglutide (Victora)

Liraglutide is other GLP 1 agonist it is injected once a day. Not used in those people with family history of medullary type of thyroid cancer.

3. Amylin agonist

Pramlintide acetate (Symlin)

Pramlintide acetate is useful for those with type 1 or type 2 diabetes who are on insulin. This is injected at mealtime,it should not be mixed with insulin in same syringe. Advantage of this drug is that it helps to achieve better control of blood sugar, mainly reduce the blood sugar spike after meals. Weight reduction is other added advantage of this drug. This is injected at mealtime. Unwanted side effects is hypoglycemia if used with insulin.

4. DPP-IV inhibitors

Sitagliptin (Januvia), saxagliptin (Onglyza), and linagliptin (Tradjenta)

All are orally active drugs taken once a day, indicated in type 2 DM, they may be combined with metformin. They wont promote weight loss. Associated with only few unwanted effects. Used with precaution in patients with kidney disease. They act by protecting the breakdown of incretin, so incretins are available for long duration for insulin stimulation.

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Screening for diabetes and prediabetes.

Diabetes is a  chronic disease that will lead to complication in multiple organs in the body on long term especially if poorly controlled. Global increase in diabetes is due to population ageing, sedentary life style, obesity and  altered dietary habits.

Type 2 diabetes remain undiagnosed until the complication develops. One third of people living with diabetes is undiagnosed. Sceening program will help in detecting early recognition of diabetes. All those people who are at high risk for developing diabetes should be screened.

Criteria for screening asymptomatic people.

(a) Individual at 45 years and above  particularly if BMI more than  25kg/m2. If normal it should be repeated at 3 yearly interval.

(b) Testing should be done in younger age  especially if they have risk factors.

1. Physically inactive.

2. First degree relatives with diabetes mellitus.

3. Members of high risk ethnic group such as African Americans, Native American, Lation, Asian American, Pacific Islander.

4. Females with history of gestational diabetes or delivered a baby more than 9 lb.

5. Females with polycystic ovarian syndrome.

6. Hypertensive  people with BP more than 140/90 mm of Hg.

7. Those with Triglyceride more than 250mg/dl or HDL cholesterol less than 35 mg/dl.

8. Previous test showed impaired glucose tolerance or fasting glucose.

9. People with  other clinical features of insulin resistance  eg. Acanthosis Nigricans.

10. People with heart disease.

Screening test

To detect future diabetes the following test are used

Fasting glucose test(FBS)

Oral glucose tolerance test ( 2 hours after taking  75gm of glucose blood test is done).

The cumulative incidence of diabetes over 5-6 yrs based on above test Normal FBS, normal oral glucose tolerance - low risk 4 - 5%.

Impaired FBS, normal oral glucose tolerance - intermediate risk 20-34%.

Normal   FBS, Impaired oral glucose tolerance - intermediate risk 20-34%.

Impaired FBS, Impaired oral glucose tolerance - 38-65%.

Blood glucose level 2 hours after food intake (postprandial blood sugar )is directly related to the mortality and morbidity in heart disease, so 2 hour oral glucose tolerance test is done as screening procedure in people with heart disease.

Fasting glucose test is more convenient to people, more reproducible and cost effective hence ADA recommend fasting blood glucose test as the screening test.

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When will you give insulin in type 2 diabetes.

The term diabetes means there is increased blood sugar level above the normal range.
There are mainly two type of diabetes .
Type 1 diabetes - Which is due to reduced insulin level in the body
Type 2 diabetes - Where the basic defect is not the reduction of insulin but due to reduced action of insulin.
In Type 1 diabetes treatment of choice is only insulin.
In Type 2 diabetes initial treatment of choice is anti diabetic tablets. Insulin is given only in the following situations

(a) Newly diagnosed symptomatic type 2 diabetes with severe hyperglycemia.
(b) Poor glucose control while taking maximal doses of a combination of oral medications.
(c) Intercurrent illness (eg - myocardial infarction, infection) or operation.
(d) Pregnancy.
(e) Kidney disease.
(f) Liver disease.
(g) Allergy to or inability to tolerate oral antidiabetic medication.

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Why exercise is advised in diabetic patients

Diabetes mellitus is a condition characterized by elevated blood sugar value. Apart from that there is alterations in blood lipid value and blood pressure. In diabetic patients exercise will help to decrease the blood sugar and also increases the sensitivity to insulin.

Other positive effect of exercise in diabetic patients

1. Decrease the heart attack risk

2. Decrease the blood pressure.

3. Exercise will help to reduce the muscle mass.

4. Reduce the body fat.

5. Produce weight loss.

Recommend exercise in diabetes

Diabetic people are advised exercise 150 minutes/week that is distributed at least over 3 days, moderate aerobic physical activity and resistance training.

Precaution before starting exercise in diabetic patients.

Since  diabetic patients are at high risk for heart disease without pain exercise tolerance test may be done in the following situations.

1. Age  more than 35 yrs

2. Duration of diabetes more than 15 yrs in type 1 diabetes and more than 10 yrs in type 2 diabetes.

3. If the patient has complications of diabetes such as kidney disease ,eye disease

4. Blood vessel occlusion in limbs.

5. Other risk factors for heart disease.

Those patients who have proliferative diabetic retinopathy should avoid vigorous exercise because of the chance of bleeding in to eye. 

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Screening for gestational diabetes mellitus - Glucose challenge test and glucose tolerance test

Gestational diabetes means diabetes first detected during the present pregnancy. Usually occur during the later half of pregnancy. Its detection and treatment is important because this can result in increased birth weight of fetus and complication during delivery.

Screening for diabetes during pregnancy.

Glucose challenge test (GCT)

How it is done ?

Patient is given 50 gms of oral glucose, as sugar syrup (dissolved in about 150 ml of water) to drink. This test is done without regard to time or last meals.

Usually done between 24 to 28 week of pregnancy.

A plasma glucose value 140 mg% or whole blood value 130 mg% is considered as cut off value and indication for  Glucose tolerance test.

Glucose tolerance test or (GTT)

Glucose tolerance test is done after taking 100 gm oral glucose (75 gm glucose as per WHO recommendation). Fasting blood sugar and blood sugar first ,second and third hour after 100 gm glucose is taken. If done after intake of 75 gms of oral glucose, fasting and 2 hour blood sugar  is taken.

Interpretation of GTT

Criteria for diagnosis of gestational diabetes with 100 gm oral glucose tolerance test.

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Skin manifestations of diabetes

In diabetes various skin manifestations are seen. The altered carbohydrate-lipid metabolism, lesions in the small blood vessels and, neural involvement all these may be associated with skin lesions. The common  skin manifestations are given below.

Infection

Most common skin manifestations in diabetes is delayed woud healing and skin ulceration. Chronic bacterial infection of the skin occur, especially in uncontrolled diabetes. There is increased chance of infection with staphylococcus, coliform, and pseudomonal infection.

Candidal infection (fungal) is more common in diabetic patients. It cause redness and edema in the area below breast, between fingers and in axilla. In uncontrolled diabetes candidal vulvovaginitis is commom. It produce pruritus.

Hypertriglyceridemia can produce Eruptive xanthomas if the glycemic control is poor.

Xerosis (dryness of skin ) and pruritus is common in diabetes, and moisturizers are used to relieve them.

Vitiligo (area of hypopigmentation ) is more common in type 1 diabetes.

Acanthosis nigricans (hyperpigmented velvety lesions seen in the neck, axilla, or extensor

surfaces) is a feature of insulin resistance

Specific skin lesions of diabetes

Diabetic dermopathy

Also called as Shin spots or diabetic skin spots They are seen in the legs over the shin and rarely on the thighs and forearms. More common in elderly men with a sex ratio 2:1, start as red area which later becomes circular hyperpigmented lesion. This  lesions is due to  minor mechanical trauma in the shin region

Granuloma annulare

They are circular raised lesion seen in the hands and feet. Other areas affected are elbow  knee and ankle. They start as raised area later fuse to form the circular lesion may be single or multiple. More common in women below 30 yrs. It may be associated with insulin dependent diabetes mellitus. This is a self limiting condition that clears over 2-3 yrs.

Necrobiosis lipoidica diabeticorum

An unusual lesion over the legs or ankle. Shin region is the most common site. It is an oval or irregular plaque with distinct bordes and glistening yellow surface. More common in women. These lesions rarely resolve.

Necrobiosis lipoidica diabeticorum

Diabetic bullae (bullosis diabeticorum seen  in longstanding diabetes  with diabetic neuropathy. They have rapid  origin seen in the toes, foot, and fingers. The blisters are tense, and the content may be serous and sometimes haemorrhagic fluid.

Lipoatrophy and lipohypertrophy may be seen at insulin injection sites but  now a days incidence is low with the use of human insulin. 

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Why insulin is given in diabetes?

Diabetes is a state of insulin deficiency. In adult diabetes is treated with either oral anti diabetic tablets or with insulin. 

Insulin has got the following advantages

1. To stop the severe catabolic state & regain lean body mass.

2. Decreases frequent infections.

3. Reduce  fetal & maternal complications  in pregnancy.

4. Prevent & delay complications of diabetes.

5. Eliminate symptoms of hypoglycemia.

6. Prevent DKA(diabetic ketoacidosis).

Principles of insulin therapy

1. To supply  sufficient insulin throughout 24 h to cover the  basal requirements

2. To provide higher boluses of insulin to match the high glucose levels  following meals .

Treatment strategies

Appropriate insulin regimen is planned based on

1. Patient’s lifestyle.

2. Age.

3. Motivation.

4. General health.

5. Self management skills.

6. Goals of treatment.
Before initiating insulin patient should be given appropriate education & support about the care & use of insulin, detection & management of  hypoglycemia.

Treatment strategies in type 1

1. Multiple Daily Injections.

2. Twice daily injections are not recommended in Type 1 DM.

3. Complementary education & support.

4. Most newly diagnosed patients with type 1 diabetes may be started on a total daily dose of 0.2 to .0.4 u/ kg / day, most will ultimately require 0.6 to 0.7 u/ kg / day.

6. During puberty > 1 IU/kg per day insulin is given

Type 2 DM (Diabetes mellitus) 

1. Initial management does not include insulin.

2. Given for patients unable to achieve good blood sugar  control with a combination of diet, exercise and OHA.

3. Goals of insulin treatment is  similar to Type1 DM

Achronym's used
DM - Diabetes mellitus.
IU/kg - Units of Drug per Kilogram of body weight.
OHA - oral hypoglycemic agents.
DKA - diabetic ketoacidosis.

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HbA1c and its correlation with blood sugar level - An info for diabetes patients

HbA1c is used for assessment of long term glucose control.This lab test reveals average blood glucose level over the past 2 to 3 months.

Major use of HbA1c

1.Assessment of optimal glycemic control in a given patient.

2.Blood glucose control status in between checkups.

This is a quality control testing. Along with regular blood glucose testing it is also used to assess the success of present treatment and help to make necessary change in the treatment.

HbA1c results are expressed as a percentage. Normal value is 4% to 6%. 1% change in HbA1c represent 30 mg/dl change in mean blood glucose value.

HbA1c and blood glucose value correlation

HbA1c value(%)	Mean blood glucose
14	380
13	350
12	315
11	280
10	250
9	215
8	180
7	150
6	115
5	80
4	50

       

<7%	Excellent control. Those who are on drugs and insulin should be aware of hypoglycemia
7%-8%	Good control. Here the aim is to get a level <7% which indicate there should be attempt for further improvement.
>8%	Poor control, indicate that diabetes is not well controlled.

Frequency of measurement of HbA1c

1.Those people who meet the treatment target it has to be measured once in 6 months

2.Those are not adequately  controlled once in 3months.

3.Special care is required in preconception care of women with diabetes initially monitor in once a month and once glucose level is controlled once in 6 to 8 weeks.This is important for maximum fertility and optimum fetal growth.

Need for strict control of diabetes

Those who have adequate control of HbA1c has lesser complication of diabetes such as

1. Eye problems

2. Kidney problems

3. Nerve related complications

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How will you identify that you have metabolic syndrome.

Identification of metabolic syndrome is important because it will help to predict the risk of future heart disease and diabetic risk. Worldwide more and more people are affected by this. This is due to change in lifestyle and food habits. Metabolic syndrome is highest among native Americans. It has got 5 components. Increased waist circumference is more in females where as fasting triglycerides and hypertension is more common in males.

Five components of metabolic syndrome are the following.

1.Central obesity(waist circumference)

2.Increased triglycerides

3.Low HDL cholesterol.

4.Diabetes mellitus

5.Hypertension

Risk factors of metabolic syndrome

1. Overweight and obesity

2. Aging

3. Heart disease

4. Diabetes mellitus

5. Sedentary lifestyle 

6. Lipodystrophy

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Insulin use - Practical points

Diabetes mellitus is a progressive, metabolic disorder where there are disturbances in carbohydrate, lipid and protein metabolism. It results from insulin deficiency and / or insulin resistance. As the global burden of diabetes is increasing number of patients on insulin also increases. All those who are on insulin must know the following practical points.

Storage of insulin

1. Stored in a cool and dark place, otherwise their potency is lost (Temperature dependent).
2. Do not keep in a freezer compartment. 
3. The vial in current use can be easily kept at room temperature in a dark place without losing any potency. 
4. Cold insulin if injected is painful.

Insulin injection sites

• Absorption of insulin shows regional difference
  Absorption of insulin is maximum from abdominal region followed by upper outer arms, buttocks and upper outer thighs.
• Abdominal region > upper outer arm and buttocks > upper outer thighs
• The site of injection should be rotated within the same area.
• Depth of injection – subcutaneous with insulin syringe.
• Intravenous injection (direct injection into vein), Intravenous infusion , or Intramuscular routes (direct injection into muscle ) are used only during, emergency such as  ketoacidosis or stressful conditions.
• Same site is used for at least one month and rotation is done within the same site rather than rotating to different sites.
• Using same site decreases variability in day to day absorption. 
• Rotation within the same area prevents lipodystrophy.
• Avoid a site with open wounds or blisters.

Injection technique

• If site is clean, there is no need to clean the site with alcohol or spirit. 
• In thin or averagely built person, lift or grasp a fold of skin between thumb and index finger and inject at 45° or 90°.
• In obese person, full length injection at 90° is recommended.
• Mixing – usually available as premixed form.
• Regular insulin can be mixed with all other preparations.
• Insulin glargine should not be mixed with other insulin.

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Causes of hypoglycemia in diabetic patients

Hypoglycemia is common problem seen in diabetic patients on insulin. It is due to imbalance between insulin requirement and administration. Highest risk is just before meals and during night. All patients on insulin and oral hypoglycemic agents should be aware of the causes  of hypoglycemia and try to avoid them.

Causes of hypoglycemia in diabetes 

Relative or absolute insulin excess.

Increased dose of insulin or insulin secretagogue (agents that help to increase insulin secretion) such as sulfonylureas and meglitinides which stimulate insulin secretion.

Intake of glucose is reduced.

• Missed or delayed meals.
• Insufficient carbohydrate in meals.

Increased glucose utilization.

• Vigorous exercises.

Increased sensitivity to insulin.              

• With improved glycemic control, late after exercise, in the middle of the night, weight loss. All this situation causes increased sensitivity to insulin.

Deceased glucose production.

• Alcohol intake.

Reduced clearance of insulin.

Renal failure.

Poorly decoded insulin regimen.

Lipohypertrohy at injection sites - Erratic insulin absorption from areas of fat

Gastroparesis

Malabsorption diseases

Risk  factors of hypoglycemia in diabetic patients

1. Impaired awareness of hypoglycemia-Patient fail to recognize the clinical features of hypoglycemia.
2. Strict glycemic control.
3. Extremes of age group.
4. Long duration of dm.
5. Type 2 DM treated with sulfonylureas, insulin.
6. Somogyi phenomenon.

Early morning hypoglycemia (at 3 am) followed by hyperglycemia resulting in elevated fasting blood glucose. This phenomenon is due to increased night dose of insulin.

Management of hypoglycemia

1. Primary prevention
2. Patient education
3. Frequent self monitoring
4. Use flexible drug regimens
5. Professional guidance

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