What are the cutaneous manifestation of Diabetes mellitus?

Diabetes mellitus is associated with following cutaneous manifestation

• Necrobiosis lipoidica diabeticorum is characterised by papulonodular lesions enlarging to form brownish yellow plaques with waxy surface over the front of legs.
• Diabetic dermopathy are  dull red, oval, flat-topped papules over both legs
• Diabetic bullae are seen the over legs, hands and feet bilaterally and  healing with atrophic scars.
• Diabetic rubeosis is the flushed skin of face.
• Scleredema diabeticorum is a diffuse, waxy nonpitting induration_of skin particularly over back of the neck and upper trunk
• Carotenoderma is the yellowish tint of skin due to deposition of carotene
• Granuloma annulare is characterised by the papular lesion over central areas of body and flexures of neck, arm and thigh.
• Infections like furuncle, carbuncle, candidalparonychia, balanoposthitis, intertrigo, recurrent dermatophytosis are common in diabetic patients

What are the newer hypoglycemic agents ?

The newer hypoglycemic agents act based on Incretin effect.Incretins are neuroendocrine substances that are released from GIT and increases the intestinal absorption of glucose and insulin release from pancreas.

They are of  two types

Glucagon like peptide 1(GLP1) that is degraded by dpp 

Glucose dependant insulinotropic peptide

GLP

GLP increases the glucose dependant insulin secretion only when the blood glucose >70  so, hypoglycemia not a problem with these agents.Following are the mechanism of actions of GLP

• Supress glucagon secretion
• Inhibit gastric emptying
• Decrease appetite & food intake

There are incretin mimetics and incretin enhancers

Incretin mimetics 

Incretin mimeters are degradation resistant GLP 1 R agonist

EXENATIDE

LIRAGLUTIDE

They can be given through S/C injection

Incretin enhancers

The incretin enhancers act by inhibiting DPP-4 activity

SITAGLIPTIN

VILDAGLIPTIN

They are available as oral preparations

Advantages of these newer incretin based therapy are 

This is associated with decreased risk of hypoglycemia

They help in B cell restoration upto 30%

Cytoprotective effect is also observed 

Helps to reduce weight .

Lipid friendly action is seen with incretin based therapy

They are able to combat the post prandial hyperglycemia that is produced by glucagon

Adverse effects Exenatide are 

Pancreatitis,

Anorexia,

Vomiting

Role of Amyelin in treatment of diabetes

Amyelin is a β cells product to supress α cells

Hence Synthetic amylin analogues are used to decreases α action 

These agents help to lower the postprandial hyperglycemia

Amyelin exerts centrally mediated anorectic action

This can be used as an adjuvant to insulin/SU/Metformin 

PRAMLINTIDE 

What are different Insulin preparations?

Various insulin preparations are available based on onset and duration of action.They can be short acting or long acting.

1. Lispro

Short acting group insulin.

28th lysine & 29th proline in B chain is reversed by recombinant DNA technology.

It has less tendency to form local aggregates.

Lispro has less incidence of hypoglycemia.

Absorption is delayed with NPH insulin, but not with ultralente.

Injected just before or after food.

2. Aspart

This is the shortest acting group of insulin.

This can be protaminated to extend the duration of action.

Aspart + protaminated aspart = Biphasic insulin.

Can be used as 30/70 insulin.

Used in pen devices.

3. Glulisine

Short acting insulin.

Not commonly available.

Asparagine @ B23 position is replaced by Lysine, lysine at B29 replaced by Glutamic acid.

4. Isophane / NPH insulin

Biphasic isophane available as pen devices.(Mixtard 30 novolet).

Most popular in 30/70 combination.

Lente available as Monotard.

Can be used once daily.

Ultara lente not available now.

5. Glargine

Asparagine at 21 replaced by Glycine.

2 Arginine residues added to c terminus of B chain.

Longest acting.

No peak in action,smooth sustained effect.

Less chance of hypoglycemia.

Not stable at room temp.

Cant mix with others.

6. Detemir

Myristic acid is bound to B29 lysine.

Long acting.

No local aggregate is formed.

Bound to albumin.

Less chance of hypoglycemia.

7. Degludec

Newer Long acting.

Effective at physiological pH.

Can be mixed with other insulins.