DIABETESTypes & Treatments

KARTIKEY VIKRAM SINGH

B.Tech IVth YEARRoll no. 1014354022

DIABETES MELLITUS Diabetes mellitus, or simply diabetes, is a

group of metabolic diseases in which a person has high blood sugar, either because--

1. The pancreas does not produce enough insulin.

2. Cells do not respond to the insulin that is produced.

This high blood sugar produces the classical symptoms of –

Polyuria (frequent urination)

polydipsia(increased thirst)

polyphagia (increased hunger).

Type 1 Diabetes mellitus

Type 1 Diabetes mellitus

Characterized by loss of the insulin-producing beta cells of the islets of Langerhans in the pancreas, leading to insulin deficiency.

immune-mediated or idiopathic. The majority of type 1 diabetes is of the immune-mediated nature, in which beta cell loss is a T-cell mediated autoimmune attack.

There is no known preventive measure against type 1 diabetes. Most affected people are otherwise healthy and of a healthy weight when onset occurs.

Type 1 diabetes can affect children or adults, but was traditionally termed "juvenile diabetes" because a majority of these diabetes cases were in children.

Type 2 Diabetes Mellitus Type 2 diabetes is a condition where the body is

insulin deficient or has a resistance to the action of insulin.

Characterized by insulin resistance, which may be combined with relatively reduced insulin secretion.

The defective responsiveness of body tissues to insulin is believed to involve the insulin receptor. However, the specific defects are not known.

Diabetes mellitus cases due to a known defect are classified separately. Type 2 diabetes is the most common type.

In the early stage of type 2, the predominant abnormality is reduced insulin sensitivity. At this stage, hyperglycemia can be reversed by a variety of measures and medications that improve insulin sensitivity or reduce glucose production by the liver.

Other Types

Besides above mentioned types there are some other also which occurs at certain condition:-

1. Gestational Diabetes

2. LADA

( Latent autoimmune diabetes of adults)

Diabetes Nutrition and Complications Trial

A total of 192 diabetic subjects attending four centres (HCSC, CSCH, CPH, and HGA) between 1993 and 2000 completed the study.

Ninety-three had type 1 diabetes mellitus (41 men, 34.7+-15.1 years old and 20.1+-9.5 years of diabetes duration; 52 women, 36.7+-12.8 years old and18.9+-10.1 years of diabetes duration).

Ninety-nine had type 2 diabetes (42 men, 66.6+-8.6 years old and disease duration of 17.1+-7.7 years; 57 women, 66.3+-11.0 years old and diabetes duration of 18.0+-8.6 years).

The Diabetes and Nutrition Study Group of the Spanish Diabetes Association (GSEDNu)

Complications

damage to blood vessels.

doubles the risk of cardiovascular disease. The main “macrovascular” disease(related to atherosclerosis of larger arteries).

ischemic heart disease(angina and myocardial infarction), stroke and peripheral vascular disease.

Microangiopathy.

Diabetic retinopathy which affects blood vessel formation in the retina of the eye.

Diabetic nephropathy, the impact of diabetes on the kidneys, can lead to scarring changes in the kidney tissue.

Diabetic neuropathy, the impact of diabetes on the nervous system.

Several studies suggest a link between cognitive deficit and diabetes.

EPIDEMICS

Globally, as of 2010, an estimated 285 million people had diabetes, with type 2 making up about 90% of the cases.

Its incidence is increasing rapidly, and by 2030, this number is estimated to almost double.

Diabetes mellitus occurs throughout the world, but is more common (especially type 2) in the more developed countries. The greatest increase in prevalence is, however, expected to occur in Asia and Africa, where most patients will probably be found by 2030.

Prevalence of diabetes worldwide in 2000 (per 1,000 inhabitants) - world average was 2.8%

TREATMENTFor Type I DM

Diagnosis

Fasting plasma glucose level ≥ 7.0 mmol/l (126 mg/dl)

Plasma glucose ≥ 11.1 mmol/l (200 mg/dL) two hours after a 75 g oral glucose load as in a glucose tolerance test

Symptoms of hyperglycemia and casual plasma glucose ≥ 11.1 mmol/l (200 mg/dl)

Glycated hemoglobin (Hb A1C) ≥ 6.5%.

Condition 2 hour glucose Fasting glucose HbA1c

 mmol/l(mg/dl) mmol/l(mg/dl) %

Normal <7.8 (<140) <6.1 (<110) <6.0

Impaired fasting glycaemia <7.8 (<140) ≥ 6.1(≥110) & <7.0(<126) 6.0–6.4

Impaired glucose tolerance ≥7.8 (≥140) <7.0 (<126) 6.0–6.4

Diabetes mellitus ≥11.1 (≥200) ≥7.0 (≥126) ≥6.5

If diagnosis confirms the condition of Diabetes mellitus then medication for reversal of the condition will be given.

A specific life will be advised to the patient and the diet will be also controlled according to the requirement.

The constituent of the diet we be modified according to the condition of the patient.

It is result of autoimmune disease hence no specific treatment is present.

But researches has shown that transplantation of beta cells form healthy donor can decrease the dependence on the Oral insulin.

Humulin R and Novolin R (regular)

Oral insulin was given to the patients who were facing the shortage of this enzyme in the body but sensitivity was still intact for its reception.

Treatment Type2DM

Treatment for type 2 diabetes can include:

insulin tablets or injections

maintaining a healthy lifestyle which includes a healthy diet and regular exercise

Cell-based therapies

In vivo Islet of Langerhans in pancreas

Replacement cells for diabetes

Type I diabetes transplant of new pancreas cells.

In type I DM reformation of beta cells may lead to permanent cure of the disease.

Inducing the receptors and transporters may also effect the type 2 DM.

Using stem cells and growing them to produce the insulin in the IN VIVO system may eliminate the injections.

In pancreatic β cells, the endoplasmic reticulum (ER) is an important site for insulin biosynthesis and the folding of newly synthesized proinsulin. Here, we show that IRE1α, an ER-resident protein kinase, has a crucial function in insulin biosynthesis. (Rhodes, 2004;Rhodes et al., 2005)

IRE1α phosphorylation is coupled to insulin biosynthesis in response to transient exposure to high glucose; inactivation of IRE1asignaling by siRNA or inhibition of IRE1aphosphorylation hinders insulin biosynthesis. IRE1 activation by high glucose does not accompany XBP-1 splicing and BiP dissociation but upregulates its target genes such as WFS1.

• Binding of insulin causes transphosphorylation of tyrosines on the receptor Phoshotyrosine residues bind IRS-1 (insulin receptor substrate – adapter protein)

• Active PKB is released into the cytosol�� Where it translocates glucose transporter �GLUT4 to the Membrane

• Increases glucose uptake

conclusion

Diabetes is not a single disease but a cumulative metabolic failure .

So to cure this we have to focus simultaneously on many factors but pancreas will be common in all.

Cellular therapies are more promising than the chemical ones

The number of functionally intact ß cells in the islet organ is of decisive importance for the development, course and outcome of diabetes mellitus. Generally speaking, the total ß-cell mass reflects the balance between the renewal and loss of these cells. Assuming that virtually all forms of diabetes mellitus are characterized by an insufficient extent of beta cell replication needed to compensate for the loss or dysfunction of beta cells occurring in diabetes, elucidation of the regenerating potential in experimentally induced diabetic animal would be of interest as alternative therapy for diabetes.

References Rhodes, C.J., Shoelson, S., and Halban, P.A. (2005). Insulin

Biosynthesis,Processing, and Chemistry. In Joslin’s Diabetes Mellitus, C.R. Kahn, G.C.Weir, G.L. King, A.M. Jacobson, A.C. Moses, and R.J. Smith, eds. (Boston:Joslin Diabetes Center), pp. 65–82

A.M. jamesshapiro, M.B., B.S., Jonathanr.t. lakey, ph.d., Edmonda. ryan, M.D the new england journal of medicine,islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen volume 343 july 27, 2000.

Kathryn L. Lipson, Sonya G. Fonseca, Shinsuke Ishigaki, Linh X. Nguyen, Elizabeth Foss, Rita Bortell, Aldo A. Rossini and Fumihiko Urano Regulation of insulin biosynthesis in pancreatic beta cells by an endoplasmic reticulum-resident protein kinase IRE1 University of Massachusetts Medical School, Worcester, Massachusetts 01605.

Research and Clinical Practice, Volume 58, Issue 3, December 2002, Pages 155-165 Makarand V Risbud, Ramesh R Bhonde.

Research and Clinical Practice, Volume 101, Issue 1, July 2013, Pages 1-9

American Diabetes Association. (2003a). Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications (Position Statement). Diabetes Care, 26 (Suppl. 1), s51 – s61.

The Diabetes and Nutrition Study Group of the Spanish Diabetes Association (GSEDNu). (2004b). Diabetes Nutrition and Complications Trial (DNCT): Trends in nutritional pattern between 1993 and 2000 and targets of diabetes treatment in a sample of Spanish people with diabetes.Diabetes Care, 27, 984 – 987.

Wild S, Roglic G, Green A, Sicree R, King H (2004). "Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030". Diabetes Care 27 (5): 1047–53.doi:10.2337/diacare.27.5.1047. PMID 15111519.

Williams textbook of endocrinology (12th ed.). Philadelphia: Elsevier/Saunders. pp. 1371–1435. ISBN 978-1-4377-0324-5.