AUTHOR:-DR  PREMANIDHI PANDA,                                           
M.D(MED),HON PhD IN DIABETES(USA),MRCP,FRCP
DIRECTOR,Prof. Panda DIABETES INSTITUTE( INDIA)
SUMMERY:-
Usually patients with type 2 diabetes will eventually fail to respond adequately to oral hypoglycaemic drugs in term  therapyFirst line of  drug  is in my study Metformin plus  Suphonylurea or with Gliptin therapy  and will require insulin therapy. Usally  at that situation  an Ultra Long Basal Insulin Like Glarigine(LANTUS)or  Insulin detemir (Levemir) at  bedtime  before dinner  or Human Mixtard (NOVO MIXTARDS EFFECTS  BETER THAN OTHERS) given twice a day with daytime oral drugs is giving  good result with  good  control of  glycemic control. It can be started safely in general practice with a good result.
Insulin is a peptide hormone produced by beta cells in the pancreas. It regulates the metabolism of carbohydrates and fats by promoting the absorption of glucose from the blood to skeletal muscles and fat tissue and by causing fat to be stored rather than used for energy. Except in the presence of the metabolic disorder diabetes mellitus and metabolic syndrome.
Insulin  is divided  as follows:-
Rapid Acting Insulin:-

• Regular insulin (Humulin R, Novolin R)
• Insulin lispro (Humalog)
• Insulin aspart (Novolog)
• Insulin glulisine (Apidra)
• Prompt insulin zinc (Semilente, Slightly slower acting)

Examples of intermediate acting insulins include

• Isophane insulin, neutral protamine Hagedorn (NPH) (Humulin N, Novolin N)
• Insulin zinc (Lente)

Examples of long acting insulins include

• Extended insulin zinc insulin (Ultralente)
• Insulin glargine (Lantus)
• Insulin detemir (Levemir)

Diabetes mellitus type 2 (formerly noninsulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes) is a metabolic disorder that is characterized by hyperglycaemia (high blood sugar) in the context of insulin resistance and relative lack of insulin. This is in contrast to diabetes mellitus type 1, in which there is an absolute lack of insulin due to breakdown of islet cells in the pancreas. Most people who are newly diagnosed with type 2 diabetes are usually treated with a combination of diet, exercise, and an oral medication .If the blood sugar  does not control  and if HBA1C is >8.5.Insulin has to be added. In my clinical practice    I prefer Oral drugs plus Glarigine(LANTUS).But  very few cases I have added NOVO HUMAN MIXTARD twice daily.I have never used the Insulin 0.3Unita to 0.6 Units/kg body weight.I still now using  sliding scale I have never found Hypoglycemia.In case of  Ultralong Basl Insulin:-I have started :-

• <150 Nil
• 150-170   2Units
• 170-190   4Units
• 190-210   6Units SO ON.
• But For  Human Mixtard:-
• <120  Nil
• 120-140  2Units
• 140-160   4Units So on..

Type 2 diabetes mellitus is associated with insulin resistance and slowly progressive beta-cell failure. By the time type 2 diabetes is diagnosed in patients, up to one-half of their beta cells are not functioning properly. 3 Beta-cell failure continues at a rate of about 4 percent each year. 4Therefore, patients with type 2 diabetes often benefit from insulin therapy at some point after diagnosis.
Pain, weight gain, and hypoglycemia may occur with insulin therapy. Pain is associated with injection therapy and glucose monitoring, although thinner and shorter needles are now available to help decrease pain. Weight gain  associated  with insulin therapy is due to the anabolic effects of insulin, increased appetite, defensive eating from hypoglycemia, and increased caloric retention related to decreased glycosuria. In the U.K. Prospective Diabetes Study, patients with type 2 diabetes who were taking insulin gained an average of 8 lb, 13 oz (4 kg), which was associated with a 0.9 percent decrease in A1C level compared with patients on conventional therapy.5Hypoglycemia may occur from a mismatch between insulin and carbohydrate intake, exercise, or alcohol consumption. Hypoglycemia has been associated with an increased risk of dementia and may have implications in cardiac arrhythmia.  All patients should be instructed on the symptoms  and treatment of hypoglycaemia.I  recommend that the blood glucose level be checked if hypoglycemia is suspected (glucose level lower than 70 mg per dL , then treated with a fast-acting carbohydrate, such as juice or glucose tablets. The blood glucose level should be rechecked after 15 minutes to make sure it has normalized.In my study  for last more than 10years I  could not find any Cancer   with Glarigine.Here I am adding that  I am dead against banning Pioglitazone  which  should not be  because  its a good molecule particularly reducing  postprandial blood sugar.Even I am taking more than 14years.
Analogue Versus Human Insulin:-
Glucose control, adverse effects, cost, adherence, and quality of life need to be considered when choosing a type of insulin. In general, analogue insulin is similar to human insulin in controlling diabetes, although some trials have found higher mean A1C levels in patients taking analogue insulin compared with human insulin. 17 Analogue insulin usually causes less postprandial hyperglycemia and delayed hypoglycemia. In my study  Glarigine and Human Mixtard  is more effective than any Insulin.In my study  I found Even  glucose varies from company to company.NovO  is better than  any other company.
Choosing the Correct Type of Insulin:

Insulin regimens should be tailored to the patient's needs and lifestyle. One of the most important considerations is the pharmacokinetics of different insulin preparations.

Table 1.

INSULIN TYPE	ONSET	PEAK	DURATION
Long-acting
Detemir (Levemir)	3 to 4 hours	6 to 8 hours	6 to 23 hours
Glargine (Lantus)	90 minutes	None	24 hours
Intermediate-acting
NPH (Humulin N)	1 to 2 hours	4 to 10 hours	14 or more hours
Short-acting
Aspart (Novolog)	15 minutes	1 to 3 hours	3 to 5 hours
Glulisine (Apidra)	15 to 30 minutes	30 to 60 minutes	4 hours
Lispro (Humalog)	15 minutes	30 to 90 minutes	3 to 5 hours
Regular	30 to 60 minutes	2 to 4 hours	5 to 8 hours
Mixed*
NPH/lispro or aspart	15 to 30 minutes	Dual	14 to 24 hours
NPH/regular	30 to 60 minutes	Dual	14 to 24 hours

OTHER FACTORS AFFECTING INSULIN ACTION

Several factors can affect how injected insulin works.
Dose of insulin injected — The dose of insulin injected affects the rate at which the body absorbs it. Larger doses of insulin may be absorbed more slowly than smaller doses.
Site of injection — Clinicians usually recommend rotating injection sites to minimize tissue irritation. When changing sites, it is important to keep in mind that insulin is absorbed at different rates in different areas of the body.
Insulin is absorbed fastest from the abdominal area, slowest from the leg and buttock, and at an intermediate rate from the arm. This may vary with the amount of fat present; areas with more fat under the skin absorb insulin more slowly.
It is reasonable to use the same general area for injections given at the same time of the day. Sometimes abdominal injections, which are absorbed more quickly, are preferred before meals. Injection into the thigh or buttock may be best for the evening dose because the insulin will be absorbed more slowly during the night.
Smoking and physical activity — Any factors that alter the rate of blood flow through the skin and fat will change insulin absorption. Smoking decreases blood flow. In contrast, factors that increase blood flow (such as exercise, saunas, hot baths, and massage of the injection site) increase insulin absorption and can result in hypoglycemia. Therefore, to avoid low blood sugar, insulin injections should be given after a bath or sauna. It is best to inject insulin into the arm or abdomen and wait 30 minutes before running. A lower dose of insulin may be recommended before or after exercise; this should be discussed with a healthcare provider.
Time since opening the bottle — Most insulin remains potent and effective for up to a month after the bottle has been opened (if kept in the refrigerator between injections). However, the potency of intermediate and long acting insulin begins to decrease after 30 days. This can be a problem for people who   require very small doses of insulin, for whom a bottle might last two months or more. It is advisable to start a new bottle at least every 30 days.
For very rapid acting insulin used in pen injectors, it is acceptable to keep the pen injector at room temperature (in a purse or jacket pocket) for up to 14 days, provided that the pen is not exposed to temperature extremes. However, after 14 days, a new insulin cartridge or pen should be used, even if there is insulin left in the old cartridge.
Individual differences — The same dose of the same type of insulin may have different effects in different people with diabetes. Some trial and error is usually necessary to find the ideal type(s) and dose of insulin and  reqire for each person.
Insulin needs often change over a person's lifetime. Changes in weight, diet, health conditions (including pregnancy), activity level, and occupation can have an impact on the amount of insulin needed to  control of blood sugar level .Patients are often able to adjust their own insulin dose, but may require assistance in some situations. (See "Patient information: Care during pregnancy for women with type 1 or 2 diabetes mellitus (Beyond the Basics)".
Management:-
(1)LIFESTYLE  Interventions
(2)MEDICATION:- There are several classes of anti-diabetic medications available. Metformin  is generally recommended as a first line treatment.Other medications are  sulfonylurea, nonsulfonylurea secretagogues, alpha glucosidase inhibitors, thiazolidinedione, glucagon-like peptide-1 analog, and dipeptidyl peptidase-4 inhibitors.Pioglitazone, a thiazolidinedione In my view Over a period of 13years treatment to more than 25000 Patients I do not found any side effects line heart failure,Bone fracture or a single case of Bladder cancer.Its a good drug with cardiovascular saftety.

Most people do not initially need insulin. But  here  I am writing many doctors Initially  starting   Insulin for business purpose .Now a days Long acting Insulin like glarigine is best Insulin With single  dose therapy at night dose rather than  Twice daily dose.(GLARIGINE). When nightly insulin is insufficient, twice daily insulin may achieve better control. The long acting insulins glargine and detemire are equally safe and effective. and do not appear much better than neutral protamine Hagedorn (NPH) insulin.In pregnancy with type II diabetes Insulin is the main stay of therapy.

SURGERY:-
Weight loss surgery in those who are obese is an effective measure to treat diabetes. Many are able to maintain normal blood sugar levels with little or no medications following surgery and long-term mortality is decreased.
Insulin Therapy  In Type II Diabetes:- A number of landmark randomized clinical trials established that insulin therapy reduces micro vascular complications . In addition, recent follow-up data from the U.K. Prospective Diabetes Study (UKPDS) suggest that early insulin treatment also lowers macro vascular risk in type 2 diabetes .But in my practice  I did not find any difference between Insulin and  Oral Antidiabetic drugs with controlling blood sugar. controversy exists on how to initiate and intensify insulin therapy.I also object to start initially  with insulin thearapy to start with.
MY VIEW INSULIN THERAPY IN TYPE II DIABETES:- Six conditions  in type II diabetes.

•  (1)In Type II Diabetes when maximum oral hypoglycimic drug does not work.
• (2)You are having infection.
• (3)You are undergoing surgery.
• (4)When target organs involved(BRAIN,HEART,KIDNRY,NERVES)
• (5)Fulminating Conditions.
• (6)Gestational Diabetes   With Previous History of Type II diabetes.

The team says their findings apply to type 2 diabetes patients with hemoglobin A1c levels below 8.5%. But they note that patients with levels above 8.5% may be likely to see greater benefits from insulin therapy, as they are at greater risk of diabetes complications.But here  I observe with Oral tablet  there is no difference between  Insulin and Oral Antidiabetic Drugs. Still then more than 75years old If  HBA1C  more than 8.5  Insulin can be given along with Oral Drugs. Currently, we are failing our patients by not recognizing that their preferences and views of treatment burden are the most important factors in helping them make glycemic treatment decisions that are best for them.
WITH  AGE GROUP 30-70YEARS:-
In younger  diabeteics with high oral drugs with HBA1C more than 7 Insulin can be started early with life style modification  to minimize Macrovascular and Microvascular Complication when fails with oral drugs.In old person more than 75years  when HBA1C >8.5 Insulin should be started as soon as possible.
ORAL DRUGS WITH INSULIN:-
After  coming of newer  oral  drugs  particularly (1)Glimiperide(2)Pioglitazone a Wonderful drug  in my opinion(3)Voglibose I  never got any  uncontrolled blood sugar  Patient.Out of 47000 Patients 80% are within  this regimen.
I have add  Insulin  when any  younger patient having HBA1C >7 after the oral drugs .and  Older patient >8.5.I   used to prefer Ultra long Basal Insulin once before dinner . In my study I have taken in my convenient dose in sliding scale not 0.5units/Kg body weight.
<150 Nil
150-170   2Units
170-190   4Units
190-210   6Units SO ON
In my study  I have never found any hypoglycemia  except one  who has  taken  small  diet than Usual  diet. There was tremendous  result in  with blood sugar,HBA1C,Lipid Profile.
I  have conclusion do not start  InsulinInitially. Start with Oral  drugs.After  2-3months if Blood sugar will not be controlled. Add  Ultralong  Basal Insulin in sliding dose rather than Usal 0.5Units/Kg body weight.Used in sliding scale.<150 Nil,150-170 2Units,170-190 4Units and so on.OR  Human Mixtard(NOVO)  in the dose <120 NIL,120-140  4Units and so on . Use of insulin glargine(LANTUS) by giving subcutaneously  compared with  Without Lantus with three drugs  to be continued  as before is associated with less nocturnal hypoglycemia and lower post-dinner glucose levels. These data are consistent with peak less and longer duration of action of insulin glargine compared without Lantus  . Achievement of acceptable average glucose control requires titration of the insulin dose to an FBG target  110mg/dl. These data support use of insulin glargine (LANTUS)in insulin combination regimens in type 2 diabetes Who those are not controlled with Thee drug Regimen. Patients with shorter duration T2DM better achieved target A1C levels. A single subcutaneous injection of glargine at a dose  as per my  sliding scale can acutely reduce glucose, HBA1C, and LIPID PROFILE levels for 24 h in obese insulin-resistant type 2 diabetic individuals. Glargine lowers blood glucose by mainly inhibiting  EGP with limited effects on stimulating glucose disposal. Large doses of glargine have minimal effects on glucose flux and retain a relatively hepatospecific action in type 2 diabetes. Numerous studies have investigated the clinical efficacy of insulin glargine in both type 1 and type 2 diabetes. Glargine has been found to lower A1C, provide effective basal insulin replacement, and reduce the risk of hypoglycemia.

Biography:
DR PREMANIDHI PANDA,M.D(MED),HON PhD IN DIABETES,MRCP,FRCP has completed his M.B.B.S at the age of 24 years from Berhampur University, India and postdoctoral studies,M.D(MED) from UTKALUniversity School of Medicine. He is the director  of Prof. Panda DIABETES INSTITUTE,INDIA, a premier DIABETES  HOSPITAL CUM RESEARCH CENTRE,INDIA.He has worked in TISCO HOSPITAL,INDIA,BENGHAZI MEDICAL(LIBYA),MEDWIN HOSPITAL With Repute.He has been awarded as “INDIA’s BEST  DOCTOR AWARD:-2013(DIABETES)” BY MEDGATE TODAY SURVEY.He Has been Awarded MRCP,FRCP BY ROYAL COLLEGE OF PHYSICIAN AND SURGEON. He has published more than 20 papers in reputed journals and serving as Director of Prof. Panda DIABETES INSTITUTE,INDIA. He  has been awarded  several  National & International awards contribution in diabetes.
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