Diabetes mellitus

Type 1
Shreya singh
Group GM20-136
Diabetes Mellitus
• Diabetes mellitus is a heterogeneous group of
disorders characterized by persistent
hyperglycemia.
• It arises due to either a deficiency of insulin
secretion, resistance to peripheral actions of
insulin, or both.
• The etiology of diabetes mellitus includes
genetic factors that influence beta-cell
function and insulin resistance, environmental
factors such as diet and physical activity, and
in some cases, autoimmune destruction of
pancreatic beta cells.
Insulin and Its Role in Glucose
Metabolism

• Insulin is a pivotal hormone for

glucose homeostasis, facilitating
the uptake of glucose into cells,
particularly in muscle and adipose
tissue, and suppressing hepatic
glucose production.
• Insulin deficiency or dysfunction
disrupts normal glucose
metabolism, leading to elevated
levels of glucose in the blood, a
hallmark of diabetes mellitus.
Normal Glucose Homeostasis

• The regulation of blood glucose levels is

a critical physiological process.
• Insulin, secreted by pancreatic beta cells
in response to elevated blood glucose,
such as after a meal, promotes glucose
uptake by muscle and adipose tissue
and inhibits hepatic glucose production.
• Conversely, glucagon, secreted by alpha
cells when blood glucose is low,
stimulates glycogenolysis and
gluconeogenesis in the liver to increase
blood glucose levels.
Insulin Signaling
Pathway
• Insulin binds to its receptor on
target cells, triggering a signaling
cascade that facilitates glucose
transporter (GLUT4) translocation
to the cell membrane, allowing
glucose entry into the cell.
• Additionally, insulin signaling
promotes glycogen synthesis and
inhibits lipolysis and proteolysis,
conserving energy stores.
Classification of Diabetes
Mellitus
• Diabetes mellitus is classified into several categories,
with Type 1 and Type 2 being the most common.
• Type 1 diabetes results from autoimmune-mediated
destruction of insulin-producing beta cells, leading to
absolute insulin deficiency.
• Type 2 diabetes is characterised by a combination of
insulin resistance and an eventual decline in insulin
production.
• Other forms include gestational diabetes, which
occurs during pregnancy, and specific types due to
other causes, such as monogenic diabetes syndromes,
diseases of the exocrine pancreas, and drug-induced
diabetes.
Type 1 DM

• Autoimmune destruction of pancreatic β cells in genetically susceptible individuals

• HLA association: HLA-DR3 and HLA-DR4 positive patients are at increased risk of
developing T1DM.
• Associated with other autoimmune conditions
• Hashimoto thyroiditis
• Type A gastritis
• Celiac disease
• Primary adrenal insufficiency
Pathophysiology

• Genetic susceptibility and environmental triggers (often associated with

previous viral infection) → autoimmune response with production
of autoantibodies, e.g., anti-glutamic acid decarboxylase antibody (anti-
GAD), anti-islet cell cytoplasmic antibody (anti-ICA) → progressive
destruction of β cells in the pancreatic
islets → absolute insulindeficiency → decreased glucose uptake in the
tissues
Clinical features of
diabetes mellitusType 1

Onset
• Often sudden
• Diabetic ketoacidosis(DKA) is the first
manifestation in approx. one-third of
cases.
• Alternatively, children may present with
acute illness and classic symptoms.
Clinical features
• Classic symptoms of hyperglycemia
• Polyuria, which can lead to secondary enuresis and nocturia in
children
• Polydipsia
• Polyphagia
• Nonspecific symptoms
• Unexplained weight loss
• Visual disturbances, e.g., blurred vision
• Fatigue
• Pruritus
• Poor wound healing
• Increased susceptibility to infections
• Calf cramps
• A thin appearance is typical for patients with T1DM.
Diagnostics
• Hyperglycemia tests
• Random blood glucose: blood glucose measured at any time irrespective of recent meals
• Fasting plasma glucose (FPG): blood glucose measured after > 8 hours of fasting
• Inexpensive and widely available
• Should not be used to diagnose diabetes in hospitalized patients or in patients with critical illness
• Oral glucose tolerance test (OGTT): measurement of fasting plasma glucose and blood
glucose 2 hours after the consumption of 75 g of glucose
• Most sensitive test
• Less convenient and more expensive than other tests
• Hemoglobin A1C (HbA1c or A1C): glycated hemoglobin, which reflects the average blood
glucose levels of the prior 8–12 weeks
• Can be measured at any time
• Results may be altered by a variety of conditions or treatments, e.g., sickle cell trait, chronic kidney
disease.
 FPG 2-hour glucose value HbA1c
after OGTT
Diabetes mellitus ≥ 6.5%
≥ 126 mg/dL (≥ 7.0 ≥ 200 mg/dL (≥ 11.1
mmol/L) mmol/L)

Prediabetes 100–125 mg/dL (5.6– 140–199 mg/dL (7.8– 5.7–6.4%

6.9 11.0
mmol/L) = impaired mmol/L) = impaired
fasting glucose glucose tolerance
Normal < 140 mg/dL (< 7.8 < 5.7%
< 100 mg/dL (< 5.6 mmol/L)
mmol/L)
 • These tests are not routinely indicated or required to establish a diagnosis.

• C-peptide: can help differentiate between types of diabetes [30][31]

• ↑ C-peptide levels may indicate insulin resistance and hyperinsulinemia → T2DM
• ↓ C-peptide levels indicate an absolute insulin deficiency → T1DM

Additional
• Urinalysis
• Glucosuria may be present if the renal threshold for glucose is reached (nonspecific for diabetes mellitus).
• Ketone bodies: positive in acute metabolic decompensation (diabetic ketoacidosis) [31]
•

studies
Microalbuminuria: early sign of diabetic nephropathy

• Antibody testing: Consider in patients with diagnosed diabetes mellitus if there is clinical suspicion for T1DM. [25]

• Antiglutamic acid decarboxylase antibodies (Anti-GAD)

• An antibody against the enzyme glutamic acid decarboxylase, which is responsible for the conversion
of glutamic acid to GABA
• Seen in ∼ 60–80% of patients with new-onset T1DM [31]

• Anti-tyrosine phosphatase-related islet antigen 2 (IA-2) [31]

• Islet cell antibody (ICA)

Management
• Insulin Therapy
• As individuals with Type 1 diabetes mellitus (T1DM)
have an absolute deficiency of insulin, the mainstay
of treatment is lifelong insulin replacement. This is
achieved through multiple daily injections (MDI) of
basal and bolus insulin or continuous
subcutaneous insulin infusion (CSII) via an insulin
pump. The goal is to mimic physiological insulin
secretion and maintain blood glucose levels within
target ranges.
• The different types of insulin vary with respect to onset and duration
of action. Short-, intermediate-, and long-acting insulins are available.
Short-acting and rapid-acting insulins are the only types that can be
administered intravenously (IV).
• Rapid-acting insulins are used whenever a rapid onset and short
duration are appropriate (eg, before meals or when the blood glucose
level exceeds target and a correction dose is needed). Rapid-acting
insulins are associated with less hypoglycemia than regular insulin
• short-acting insulins are less commonly used than the rapid-acting
insulins in patients with type 1 DM. They are used when a slightly
slower onset of action or a greater duration of action is desired.
• Intermediate-acting insulins have a relatively slow onset of action and
a relatively long duration of action. They are usually combined with
faster-acting insulins to maximize the benefits of a single injection.
• Long-acting and ultralong-acting insulins have a very long duration of
action and, when combined with faster-acting insulins, provide better
glucose control for some patients. In patients with type 1 DM, they
must be used in conjunction with a rapid-acting or short-acting insulin
given before meals.

• Premixed insulins contain a fixed ratio of rapid-acting insulins with

longer-acting insulin, which can restrict their use. Premixed insulin is
usually not recommended in type 1 DM patients, because of their
need for frequent adjustments of premeal insulin doses.
Insulin aspart (NovoLog, Fiasp) , Insulin glulisine (Apidra), Insulin
lispro (Humalog, Admelog, insulin lispro-aabc, Lyumjev),
These Insulin have a rapid onset of action, 5-15 minutes. The peak
effect occurs within 30-90 minutes, and the usual duration of
action is 2-4 hours.
Regular insulin (Humulin R, Novolin R, Myxredlin)
Regular insulin has a short onset of action, 0.5 hour. Its peak effect
occurs within 2-4 hours, and its usual duration of action is 5-8
hours.
Insulin detemir (Levemir)
Insulin detemir is indicated for once-daily or twice-daily
subcutaneous administration in individuals with type 1 DM who
require long-acting basal insulin for hyperglycemia control. Its
duration of action ranges from 5.7 hours (low dose) to 23.2 hours
(high dose).
Insulin aspart protamine/insulin aspart (NovoLog 70/30)
The combination of insulin aspart protamine with insulin aspart includes 30%
rapid-onset insulin (ie, insulin aspart) and 70% intermediate-acting insulin (ie,
insulin aspart protamine). Insulin aspart is absorbed more rapidly than regular
human insulin, and insulin aspart protamine has a prolonged absorption
profile after injection.
Insulin lispro protamine/insulin lispro (Humalog 75/25)
The combination of insulin lispro protamine with insulin lispro includes 75%
insulin lispro protamine, which has a prolonged duration of action, and 25%
insulin lispro, which is a rapid-onset insulin.
Insulin glargine (Lantus, Lantus SoloStar, Toujeo, Toujeo Max, Basaglar)
Insulin glargine stimulates proper utilization of glucose by the cells and
reduces blood sugar levels. It has no pronounced peaks of action, because a
small amount of insulin is gradually released at a constant rate over 24 hours.
The amount of insulin in Toujeo and Toujeo Max SoloStar is three times greater
(300 Units/mL) than in Lantus or Basaglar (100 Units/mL).