07 - Diabetes Mellitus

Question 1

(D. Diabetes Mellitus)

1. Background and Classifications: Normal carbohydrate metabolism and blood glucose regulation is dependent upon adequate insulin secretion (to consume carbohydrate and lower blood glucose levels; to increase the rate of transfer of glucose into target cells to form intracellular glycogen) as well as normal regulation of insulin counter-regulatory hormones (ie., growth hormone, cortisol, glucagon, catecholamines). The syndrome of diabetes mellitus (DM) occurs when insulin secretion is insufficient to maintain blood glucose levels within the normal range. Therefore, the principal and defining test for DM is the blood (or serum or plasma) glucose level following an overnight fast. DM is not uncommon in the dog (esp. mature female dogs; higher incidence in certain small dog breeds) and cat, but is only rarely encountered in other domestic species. A relative or absolute deficiency in insulin leads to a generalized catabolic state

DM may be classified as primary or secondary. In humans, primary DM is divided into two principal forms: type 1 (insulin-dependent or juvenile onset), and type 2 (non-insulin-dependent or adult onset).

Question 2

(D. Diabetes Mellitus)

(Type 1 DM (= juvenile onset = insulin dependent in humans)

1. caused by what?
2. How quick is onset? how serious?
3. in affected human beings, the earliest islet histopathologic change iw what?
4. This condition causes an absolute deficiency and insulin is usually undetectable in the plasma of affected animals
5. The pathogenesis (in humans) is thought to be what?
6. this form accounts for how many cases in dog? cat?

Answer 2

1. immune destruction of the pancreatic islet beta cells, which produce insulin (immune-mediated isletitis)
2. rapid (weeks to months), severe - immediate therapy to prevent ketoacidosis and death
3. the influx of lymphocytes into the pancreatic islets (these cells mediate the destruction of beta cells)

(later in the course of the disease, only rare beta cells persist while other islet cell types remain in approximately normal numbers)

5. molecular mimicry in which a foreign antigen (eg: virus) is similar to a component of beta cells
6. a few; very rare

Question 3

(D. Diabetes Mellitus)

(type 2 DM (=adult onset = non-insulin dependent DM in humans)

1. most common form in humans, cats, other non-human primates… but not in what?
2. time course?
3. age?
4. develops due to what?
5. individuals with this form of DM have detectable plasma insulin, but it is insufficient to do what?
6. What is an important etiologic factor in the development?
7. is insulin resistance enough to cause type 2 DM?
8. Islets in type 2 DM are characterized by what?

9 Amyloid in the pancreatic islets is formed from what?

Answer 3

1. gods
2. long - may seem fast in cats
3. middle aged and older (8-10 cat years)
4. insuffiecient insulin secretion relative to metabolic demand
5. maintain blood glucose levels in normal range
6. insulin resistance, often secondary to obstity or derangement in counter-regulatory hormones
7. no (evidence = only minor amount of obese individuals become diabetic)
8. progressive loss of beta cells with concurrent deposition of amyloid.

(other islet cell types are relatively spared, but are also lost in very advanced lesions

9. islet amyloid polypeptide (IAPP)

IAPP is a normal 37 AA secretory product of the pancreateic beta cell, and is co-secreted with insulin. The factors that cause IAPP to from amyloid fibrils and its physiologic function are currently unknown

Question 4

(D. Diabetes Mellitus)

1. Secondary DM may occurs in dogs due to what?
2. may also occur due to what in dogs?

in cats?

Answer 4

1. chronic relapsing pancreatitis with secondary (non-specific) destruction of the pancreatic islets
2. hyperadrenocorticism

GH excess (acromegaly) due to GH-secreting pituitary tumor

Question 5

(Diabetes Mellitus)

(complications)

(diabetic ketoacidosis)

1. a life-threatening metabolic derangement cause by what?
2. Insulin deficiency increases the release of what from where?

which are converted in the liver to what?

As the discrepancy between available insulin and the metabolic need for it widens, the simtulus for lipolysis increases so that there is an increased entry of FFA into the liver.

3. In the absence of adequate glucose, hepatocellular metabolism shifts from what to what?
4. excess ketone bodies then lead to what?

Answer 5

1. insulin deficiency and counter-regulatory hormone (especially glucagon) excess
2. FFAs from adipose cells

to ketone bodies (acetone and beta-hydroxybutyric acid)

3. tyiglyceride synthesis to fatty acid oxidation
4. metabolic acidosis and ketonuria with osmotic diuresis and dehyrdration

(DKA is often triggered by intercurrent diseases or other stressful conditions)

Question 6

(Diabetes Mellitus)

(complications)

(cataracts)

1. fairly common in dogs, not in cats
2. due to what?

Answer 6

2. conversion of glucose to sorbitol and fructose in the lens

(these sugars are not freely permeable and result in osmotic swelling and destruction of lens cells)

Question 7

(Diabetes Mellitus)

(complications)

(neuropathy - peripheral demyelinating neuropathy)

1. diabetic cats may be presented with the complaint of “lameness” which is a manifestation of peripheral neuropathy. Affected cats tend to have a plantigrade stance on the hind limbs and have reduced nerve conduction velocity. Autonomic neuropathy in cats is occasionally manifest as megacolon with severe constipation.

Question 8

(Diabetes Mellitus)

(complications)

(Hepatic lipidosis - increased lipid mobilization)

Hepatic lipidosis (increased lipid mobilization), nephropathy, bacterial or fungal infections, and retinopathy. Can see microangiopathy (thickening of capillary basement membranes) and depending on the anatomic site, this can lead to blindness, chronic kidney disease (glomerulosclerosis in chronic cases), and gangrene. Role of advanced glycosylation end-products in DM: the chronic hyperglycemic state favors pro-oxidants over anti-oxidant defenses. Irreversible products accumulate on long-lived proteins (eg: lens, glomeruli, myelin). Diabetic animals also have diminished resistance to bacterial and fungal infections. Emphysematous urocystitis has been described and is associated with glucose-fermenting bacteria such as E. coli.