Diabetes mellitusPrepared for the MedicalDepartmentFranco Indian Pharmaceuticals LtdBy Dr. Ashok Moses
History• Diabetes was one of the first diseasesdescribed,[with an Egyptian manuscript from1500 BCE mentioning "too great emptying of theurine". The first described cases are believed tobe of type 1 diabetes. Indian physicians aroundthe same time identified the disease andclassified it as madhumeha or "honey urine",noting the urine would attract ants. The term"diabetes" or "to pass through" was first used in230 BCE by the Greek Appollonius of Memphis.The disease was considered as rare during thetime of the Roman empire, with Galencommenting he had only seen two cases duringhis career.
History• This is possibly due the diet and life-style of the ancientpeople, or because the clinical symptoms were observedduring the advanced stage of the disease. Galen namedthe disease "diarrhea of the urine" (diarrhea urinosa).The earliest surviving work with a detailed reference todiabetes is that of Aretaeus of Cappadocia (2nd or early3rd century CE). He described the symptoms and thecourse of the disease, which he attributed to themoisture and coldness, reflecting the beliefs of the"Pneumatic School". He hypothesized a correlation ofdiabetes with other diseases and he discussed differentialdiagnosis from the snakebite which also provokesexcessive thirst. His work remained unknown in the Westuntil the middle of the 16th century when, in 1552, thefirst Latin edition was published in Venice.
History• Type 1 and type 2 diabetes where identified asseparate conditions for the first time by the Indianphysicians Sushruta and Charaka in 400-500 CE withtype 1 associated with youth and type 2 with beingoverweight. The term "mellitus" or "from honey" wasadded by the Briton John Rolle in the late 1700s toseparate the condition from diabetes insipidus, whichis also associated with frequent urination.Effectivetreatment was not developed until the early part of the20th century, when Canadians Frederick Banting andCharles Herbert Best isolated and purified insulin in1921 and 1922.[ This was followed by the developmentof the long-acting insulin NPH in the 1940s.
Diabetes mellitus• Diabetes mellitus, or simply diabetes, is agroup of metabolic diseases in which a personhas high blood sugar, either because thepancreas does not produce enough insulin, orbecause cells do not respond to the insulinthat is produced. This high blood sugarproduces the classical symptoms of polyuria(frequent urination), polydipsia (increasedthirst) and polyphagia (increased hunger).
Diabetes mellitus• There are three main types of diabetes mellitus (DM).• Type 1 DM results from the bodys failure to produceinsulin, and currently requires the person to injectinsulin or wear an insulin pump. This form waspreviously referred to as "insulin-dependent diabetesmellitus" (IDDM) or "juvenile diabetes".• Type 2 DM results from insulin resistance, a conditionin which cells fail to use insulin properly, sometimescombined with an absolute insulin deficiency. This formwas previously referred to as non insulin-dependentdiabetes mellitus (NIDDM) or "adult-onset diabetes".• The third main form, gestational diabetes occurs whenpregnant women without a previous diagnosis ofdiabetes develop a high blood glucose level. It mayprecede development of type 2 DM.
Type 1 diabetes• Type 1 diabetes mellitus is characterized by loss of theinsulin-producing beta cells of the islets of Langerhansin the pancreas, leading to insulin deficiency. This typecan be further classified as immune-mediated oridiopathic. The majority of type 1 diabetes is of theimmune-mediated nature, in which beta cell loss is a T-cell-mediated autoimmune attack. There is no knownpreventive measure against type 1 diabetes, whichcauses approximately 10% of diabetes mellitus cases inNorth America and Europe. Most affected people areotherwise healthy and of a healthy weight when onsetoccurs.
Type 1 diabetes• Sensitivity and responsiveness to insulin are usually normal,especially in the early stages. Type 1 diabetes can affect children oradults, but was traditionally termed "juvenile diabetes" because amajority of these diabetes cases were in children.• "Brittle" diabetes, also known as unstable diabetes or labilediabetes, is a term that was traditionally used to describe todramatic and recurrent swings in glucose levels, often occurring forno apparent reason in insulin-dependent diabetes. This term,however, has no biologic basis and should not be used. There aremany reasons for type 1 diabetes to be accompanied by irregularand unpredictable hyperglycemias, frequently with ketosis, andsometimes serious hypoglycemias, including an impairedcounterregulatory response to hypoglycemia, occult infection,gastroparesis (which leads to erratic absorption of dietarycarbohydrates), and endocrinopathies (e.g., Addisons disease).These phenomena are believed to occur no more frequently than in1% to 2% of persons with type 1 diabetes.
Type 2 diabetes• Type 2 diabetes mellitus is characterized by insulinresistance, which may be combined with relativelyreduced insulin secretion.The defective responsivenessof body tissues to insulin is believed to involve theinsulin receptor. However, the specific defects are notknown. Diabetes mellitus cases due to a known defectare classified separately. Type 2 diabetes is the mostcommon type.• In the early stage of type 2, the predominantabnormality is reduced insulin sensitivity. At this stage,hyperglycemia can be reversed by a variety ofmeasures and medications that improve insulinsensitivity or reduce glucose production by the liver.
Gestational diabetes• Gestational diabetes mellitus (GDM) resemblestype 2 diabetes in several respects, involving acombination of relatively inadequate insulinsecretion and responsiveness. It occurs in about2%–5% of all pregnancies and may improve ordisappear after delivery. Gestational diabetes isfully treatable, but requires careful medicalsupervision throughout the pregnancy. About20%–50% of affected women develop type 2diabetes later in life.
Other types• Prediabetes indicates a condition that occurs when apersons blood glucose levels are higher than normalbut not high enough for a diagnosis of type 2 DM.Many people destined to develop type 2 DM spendmany years in a state of prediabetes which has beentermed "Americas largest healthcare epidemic."• Latent autoimmune diabetes of adults (LADA) is acondition in which type 1 DM develops in adults.Adults with LADA are frequently initially misdiagnosedas having type 2 DM, based on age rather thanetiology.
Pathophysiology• Insulin is the principal hormone that regulates uptake of glucose from theblood into most cells (primarily muscle and fat cells, but not centralnervous system cells). Therefore, deficiency of insulin or the insensitivityof its receptors plays a central role in all forms of diabetes mellitus.• Humans are capable of digesting some carbohydrates, in particular thosemost common in food; starch, and some disaccharides such as sucrose,are converted within a few hours to simpler forms, most notably themonosaccharide glucose, the principal carbohydrate energy source usedby the body. The rest are passed on for processing by gut flora largely inthe colon. Insulin is released into the blood by beta cells (β-cells), found inthe islets of Langerhans in the pancreas, in response to rising levels ofblood glucose, typically after eating. Insulin is used by about two-thirds ofthe bodys cells to absorb glucose from the blood for use as fuel, forconversion to other needed molecules, or for storage.
Pathophysiology• Insulin is also the principal control signal for conversionof glucose to glycogen for internal storage in liver andmuscle cells. Lowered glucose levels result both in thereduced release of insulin from the β-cells and in thereverse conversion of glycogen to glucose whenglucose levels fall. This is mainly controlled by thehormone glucagon, which acts in the opposite mannerto insulin. Glucose thus forcibly produced from internalliver cell stores (as glycogen) re-enters thebloodstream; muscle cells lack the necessary exportmechanism. Normally, liver cells do this when the levelof insulin is low (which normally correlates with lowlevels of blood glucose).
Pathophysiology• Higher insulin levels increase some anabolic("building up") processes, such as cell growthand duplication, protein synthesis, and fatstorage. Insulin (or its lack) is the principalsignal in converting many of the bidirectionalprocesses of metabolism from a catabolic toan anabolic direction, and vice versa. Inparticular, a low insulin level is the trigger forentering or leaving ketosis (the fat-burningmetabolic phase
Pathophysiology• When the glucose concentration in the blood is raised toabout 9-10 mmol/L (except certain conditions, such aspregnancy), beyond its renal threshold (i.e. when glucoselevel surpasses the transport maximum of glucosereabsorption), reabsorption of glucose in the proximal renaltubuli is incomplete, and part of the glucose remains in theurine (glycosuria). This increases the osmotic pressure ofthe urine and inhibits reabsorption of water by the kidney,resulting in increased urine production (polyuria) andincreased fluid loss. Lost blood volume will be replacedosmotically from water held in body cells and other bodycompartments, causing dehydration and increased thirst.
DiagnosisDiabetes diagnostic criteria• Fasting plasma glucose level ≥ 7.0 mmol/l(126 mg/dl)• Plasma glucose ≥ 11.1 mmol/l (200 mg/dL) twohours after a 75 g oral glucose load as in aglucose tolerance test• Symptoms of hyperglycemia and casual plasmaglucose ≥ 11.1 mmol/l (200 mg/dl)• Glycated hemoglobin (Hb A1C) ≥ 6.5%.[
Lifestyle• There are roles for patient education, dieteticsupport, sensible exercise, with the goal ofkeeping both short-term and long-term bloodglucose levels within acceptable bounds.• In addition, given the associated higher risksof cardiovascular disease, lifestylemodifications are recommended to controlblood pressure
Support• In countries using a general practitionersystem, such as the United Kingdom, care maytake place mainly outside hospitals, withhospital-based specialist care used only incase of complications, difficult blood sugarcontrol, or research projects. In othercircumstances, general practitioners andspecialists share care of a patient in a teamapproach. Home telehealth support can be aneffective management technique.