HEA 3071 Module 1 Type 2 Diabetes Case Study: Insulin Resistance, Beta-Cell Failure and Prevention Example

Too Much Sugar, Too Little Signal: The Pathophysiology of Type 2 Diabetes in a Vineland Cook

Student Name

B.S. in Health Studies, Thomas Edison State University

HEA-3071: Pathophysiology for Health Professionals

Mentor Name

Month Day, Year

Too Much Sugar, Too Little Signal: The Pathophysiology of Type 2 Diabetes in a Vineland Cook

The Patient

Hector is invented for this case. He is 49, works long shifts as a line cook in Vineland, eats most meals at work and sleeps poorly. Over three months he has been very thirsty, wakes three times a night needing the bathroom and feels exhausted by midafternoon. He has lost eight pounds without trying. His mother had diabetes. At his clinic visit his body mass index is 33, his waist measures 42 inches, his blood pressure is 142/88, his fasting glucose is 168 mg/dL and his A1C is 8.4 percent. A1C reflects average glucose over about three months, and a value of 6.5 percent or higher on repeat testing meets the threshold for diabetes.

Normal Glucose Control

After a meal, rising glucose stimulates the beta cells of the pancreatic islets to release insulin. Insulin binds receptors on muscle, fat and liver cells. In muscle and fat, it brings glucose transporters up to the membrane, opening a way in for glucose. In the liver, it stops the production of new glucose and the release of stored glucose. Between meals, glucagon from alpha cells keeps the liver releasing enough glucose to supply the brain. The result is a blood glucose held within a narrow range.

What Has Changed

DeFronzo (2009) argued that several defects together produce type 2 diabetes, beginning with insulin resistance in muscle and liver and progressive failure of the beta cells. In muscle, insulin's signal inside the cell is impaired, so less glucose is taken up after a meal. In the liver, insulin fails to suppress glucose production, so fasting glucose rises. Fat cells resist insulin's effect on fat breakdown, releasing free fatty acids that worsen resistance in muscle and liver and may harm beta cells. For years the beta cells compensate by making more insulin, and glucose stays near normal. Diabetes appears when the beta cells can no longer keep up. DeFronzo also described contributions from too much glucagon, a reduced response to gut hormones called incretins, increased glucose reabsorption in the kidney and changes in brain appetite control, which together he called the ominous octet.

Explaining Hector's Signs

Hector's thirst and nighttime urination follow from the kidneys. When blood glucose rises above about 180 mg/dL, the kidneys can no longer reabsorb all the glucose filtered into the urine. Glucose then appears in the urine, and osmosis pulls water along with it, causing frequent urination. Fluid loss triggers thirst. His weight loss reflects calories lost as glucose in the urine and the breakdown of fat and muscle when cells cannot use glucose well. His fatigue reflects both dehydration and poor fuel use. His waist size points to visceral fat, which is closely linked to insulin resistance.

Could It Have Been Prevented

More than 3,200 adults with raised fasting glucose and impaired glucose tolerance were randomized to one of three arms: a lifestyle program that aimed to trim body weight by 7 percent and build up to 150 minutes of exercise weekly, metformin, or a placebo pill (Diabetes Prevention Program Research Group, 2002). Over a mean of 2.8 years, the lifestyle arm developed diabetes 58 percent less often, and the metformin arm 31 percent less often, than the placebo arm. The lifestyle program worked in every age and ethnic group. If Hector's earlier glucose levels had been checked, he might have been offered such a program.

Why Control Matters

Years of high glucose injure the tiny vessels that feed the retina, the glomeruli and peripheral nerves. In the UK Prospective Diabetes Study, nearly 3,900 people with newly diagnosed type 2 diabetes were assigned either to tight control using a sulfonylurea or insulin or to the conventional approach, which relied mostly on diet (UK Prospective Diabetes Study Group, 1998). Over ten years, median A1C sat at 7.0 percent in the intensive arm against 7.9 percent in the conventional arm, and the intensive arm had about a quarter fewer small-vessel complications, most of the difference coming from eye disease treated with laser. Heart attacks fell somewhat too, though not by enough to rule out chance while the trial ran.

Matching Treatment to Mechanism

Each treatment acts on a different defect. Weight loss and physical activity improve insulin sensitivity in muscle and liver. Metformin, the usual first drug, mainly reduces glucose production in the liver. Newer drug classes target other parts of the octet: GLP-1 receptor agonists restore the incretin effect, slow stomach emptying and reduce appetite, and SGLT2 inhibitors block glucose reabsorption in the kidney. For Hector, his clinician started metformin, referred him to a diabetes education program and discussed meals he could prepare before his shifts.

Lifespan and Social Factors

Type 2 diabetes is appearing at younger ages, including in adolescents, as obesity rises. Hector's long shifts, irregular meals, poor sleep and family history each add risk. Hispanic adults have higher rates of type 2 diabetes than non-Hispanic white adults, and access to education and healthy food shapes how well the disease can be controlled.

Complications Over Time

If Hector's glucose stays high, damage will accumulate in two kinds of vessels. Small-vessel or microvascular damage affects the retina, the kidney's filters and the nerves of the feet, and large-vessel damage speeds atherosclerosis in the heart, brain and legs. Numb feet combined with poor circulation explain why foot ulcers and amputations are feared complications.

Limits

The prevention trial enrolled people with prediabetes in a research setting with intensive support. UKPDS used older drugs and targets. Hector is invented, and treatment for any person depends on a clinician's assessment.

Conclusion

Hector's diabetes developed over years as insulin resistance in his muscle, liver and fat outpaced the ability of his beta cells to compensate. His thirst, urination and weight loss follow directly from glucose spilling into his urine. Lifestyle change might have prevented it, and controlling his glucose now will protect his eyes, kidneys and nerves. Treatment that targets each failing mechanism is the logic pathophysiology makes possible.

References

DeFronzo, R. A. (2009). From the triumvirate to the ominous octet: A new paradigm for the treatment of type 2 diabetes mellitus. Diabetes, 58(4), 773-795. https://doi.org/10.2337/db09-9028

Diabetes Prevention Program Research Group. (2002). Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. New England Journal of Medicine, 346(6), 393-403. https://doi.org/10.1056/NEJMoa012512

UK Prospective Diabetes Study Group. (1998). Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). The Lancet, 352(9131), 837-853. https://doi.org/10.1016/S0140-6736(98)07019-6