Given this patient is elderly with multiple end stage chronic diseases, the goal of diabetes therapy is to minimize any significant hypoglycemic events that may be occurring. The target HbA1C can be adjusted to <8.0-8.5% in these patients with a less stringent fasting and preprandial blood sugar goal of 100-180 mg/dL. Since he has ESRD, sulfonylureas can predispose patients on dialysis to hypoglycemia and should be used very cautiously especially while on insulin therapy.

In older adults treatment goals for glycemic control should be modified over time based on comorbidities, functional and cognitive status, and patient/caregiver preferences.

Reference:

Standards of Care

12. Older Adults: Standards of Medical Care in Diabetes—2021

1. American Diabetes Association

Diabetes Care 2021 Jan; 44(Supplement 1): S168-S179.https://doi.org/10.2337/dc21-S012

This patient has a Hba1c of 8.0. He is obese and currently does not have any CV complications. The best treatment option for him would be to choose a medication that will address not only his high glucose but also his obesity and risk of complications.

The first choice for a second-line therapy by the new American Diabetes Association/European Association for the Study of Diabetes (ADA/EASD) guidelines is GLP1 RAs or SGLT-2 inhibitors for patients with atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease. For patients without these conditions, the ADA/EASD lists five options of noninsulin second-line therapy. On the other hand, the 2019 consensus statement from the American Association of Clinical Endocrinologists/American College of Endocrinology lists nine options, with GLP1 RAs as the first recommended therapy, followed by SGLT2 inhibitors and dipeptidyl peptidase 4 (DPP4) inhibitors, and sulfonylurea as the last option.

Currently Trulicity is the only GLP-1 agent that in addition to improving glucose and having the weight loss benefit will also provide primary prevention for CV disease.

Adding basal / bolus regime is currently not needed as many other options are available. Moreover, adding insulin will not provide the weight loss benefit and primary prevention CV benefit.

-Adding SGLT-2 inhibitor may be a good option however based on the above guidelines and primary prevention benefit associated with Trulicity once weekly GLP-1 seems like the best option.  And it will also help him lose weight.

References:

1-Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC.

2-Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double‐blind, randomised placebo‐controlled trial. Lancet. 2019;394(10193):121‐130.

3-Gerstein HC, Colhoun HM, Dagenais GR, et al. Design and baseline characteristics of participants in the Researching cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial on the cardiovascular effects of dulaglutide. Diabetes Obese Metab. 2018;20(1):42‐49.

Lifestyle modifications are important and should be optimized regardless of treatment modality but should be adjunct to other therapy modifications given the importance of achieving target as soon and safe as possible. 

Gliclazide may help improve his diabetes control but will put him at risk of hypoglycemia which can be detrimental in his condition. Also, Gliclazide promotes weight gain which is better avoided in this patient.  

Switching to a GLP1RA is a reasonable option especially with the cardiovascular benefits, however, most likely GLP1RA cause nausea, at least during the initiation period and are given as SC injections which can reduce compliance.  

Given the late presentation of his inferior MI and the mild rise in NT-pro-BNP the risk of heart failure is high. Dapagliflozin, and SGLT2 inhibitor with diuretic and glucosuric properties, would suit the patient very well with proven cardiovascular benefits including heart failure, ease of intake (oral), minimal risk of hypoglycemia, and weight reduction potential. 

Canagliflozin is an SGLT2 inhibitor that has been approved by the FDA to reduce the risk  of major cardiovascular events in adults with type 2 diabetes and established cardiovascular disease¹.  Moreover, it is also indicated to reduce the risk of end-stage kidney disease, doubling of serum creatinine, cardiovascular death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria. Relative to placebo, participants who received canagliflozin in the CREDENCE trial experienced a 30%  reduction in the risk of the primary composite endpoint, which included end-stage kidney disease, doubling of serum creatinine, and renal or cardiovascular death².

Dulaglutide is a once weekly injectable glucagon-like peptide-1 receptor agonist (GLP-1 RA). It received FDA approval for the reduction of major cardiovascular events (MACE) in adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors³. Long-term use of dulaglutide is also associated with reduced composite renal outcomes - defined as the first occurrence of new macroalbuminuria (UACR >33·9 mg/mmol), a sustained decline in eGFR of 30% or more from baseline, or chronic renal replacement therapy -  in people with type 2 diabetes⁴. Nevertheless, dulaglutide would be an unsuitable option in this scenario due to the presence of gastroparesis. GLP-1 RAs slow down gastric emptying and could therefore exacerbate gastroparesis.

Saxagliptin, a DPP4 inhibitor, is unsuitable for the lady in question, who has experienced systolic congestive heart failure exacerbations. Results from the SAVOR-TIMI 53 trial demonstrated an increased risk of heart failure hospitalization with the use of saxagliptin⁵.

Increasing the dose of Lantus would be a reasonable option, but not the best next step. As it is, she already experiences some degree of hypoglycemia. Thus, increasing the dose of insulin could increase the frequency of hypoglycemic episodes. Furthermore, monotherapy with insulin would not address the presence of CKD secondary to diabetic nephropathy or cardiovascular disease.

References:

1. Nea B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. New England Journal of Medicine. 2017;377(7), 644-657.
2. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. New England Journal of Medicine. 2019;380(24), 2295-2306.
3. Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. The Lancet. 2019;394(10193), 121-130.
4. Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial. The Lancet. 2019;394(10193), 131-138.
5. Udell JA, Bhat DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes and moderate or severe renal impairment: observations from the SAVOR-TIMI 53 Trial. Diabetes Care. 2015;38(4), 696-705.

Continuous glucose monitoring (CGM) will be of great utility for this lady during her pregnancy. Intensification of therapy is required in order to achieve HbA1C target of <6.5% and postprandial glucose target of <120 mg/dL (6.7 mmol/L) (Management of Diabetes in Pregnancy: Standards of Medical Care in Diabetes—2020, https://doi.org/10.2337/dc20-S014). CGM can enable close glucose monitoring as well as alarms for hyperglycemia and hypoglycemia which would be particularly useful for this lady given her hypoglycemia awareness impairment. The CONCEPTT trial (Feig et al, Lancet 2017, DOI: 10.1016/S0140-6736(17)32400-5) demonstrated significant reduction in maternal hyperglycemia and improved neonatal outcomes with CGMs use in comparison to standard of care.

Insulin Detemir is licensed for use during pregnancy, and while longer acting insulin analogues have evidence for hypoglycemia risk reduction the patient can achieve better outcomes by avoiding lipohypertrophy sites when injecting insulin. Sensor augmented pump can reduce risk of hypoglycemia, but given patient’s previous experience it is not recommended to explore this again in pregnancy unless recurrent hypoglycemia becomes problematic. The patient is doing carbohydrates counting already and a refresher training session will be helpful but not likely to make a difference on its own.

The diagnosis of diabetic kidney disease is based on the presence of albuminuria, defined as UACR > or equal to 300, or UACR 30-299 mg/g WITH the presence of diabetic retinopathy and/or having type 1 diabetes greater than or equal to 10 years in duration, OR demonstrated reduced kidney function and the presence of diabetes as defined as an sGFR <60 mL/min/1.73m2-.,of course, in the absence of any other causes of kidney damage.

The risk of congenital defects is clearly related to hyperglycemia in the first trimester. A meal plan that may minimize postprandial excursions could be achieved by redistribution of carbohydrate intake into three small-to-moderate meals and 2-4 snacks, with a meal plan calculated as 30 kcal per kg. During preconception planning, the Endocrine Society recommends obtaining an HbA1c as close to normal as possible, if this can be safely achieved. For women with pre-existing diabetes, the American Diabetes Association recommends attempting to optimize glycemic control prior to conception, with a goal of HbA1c <6.5%, a level associated with the lowest risk of congenital anomalies. Glycemic control later in pregnancy affects the risk for large-for-gestational age (size) and other complications. In the later stages of pregnancy, the HbA1c normally declines. As a result, the American Diabetes Association recommends a target of 6-6.5% for pregnant women with diabetes as pregnancy progress, although <6% may be optimal, with precautions to avoid hypoglycemia. The following targets are suggested:

• Fasting: ≤ 95 mg/dL
• One-hour postprandial: ≤140 mg/dL
• Two-hour postprandial: ≤ 120 mg/dL

A fasting target = 90 mg/dL is considered optimal if it can be safely achieved, with the caveat that significant hypoglycemia could be reason to modify the targets.

Because of the risk of teratogenic effects, ACE inhibitors and angiotensin receptor blocker (ARB) therapy should be discontinued and/or replaced, if necessary for control of hypertension, as part of pre-pregnancy planning. If treatment is required, antihypertensive medications that can be used effectively and safely during pregnancy include methyldopa, labetalol, diltiazem, clonidine, and prazosin. Diuretic therapy is not recommended due to the risk of volume depletion. Statin use is similarly contraindicated in pregnancy.

The patient appears to be very engaged with her insulin pump with numerous daily glucose checks and multiple bolus administrations. Despite that, her readings are elevated, more so in the afternoon and evening. By focusing on insulin distribution, we note a major imbalance between basal and bolus insulin with majority of her total daily dose (TDD) of insulin coming from bolus insulin leaving her fire-fighting trying to catch up with high glucose. It is too early to stop insulin pump therapy as she has been on it for only 4 months so far and the problem is not with patient management. While adding CGM would help with hypoglycemia early detection and fear alleviation; at this stage the patient is doing adequate glucose monitoring and she has not had hypoglycemia while on insulin pump. The effect of adding CGM on improving diabetes control would be minimal as the problem is not lack of monitoring. Switching to a sensor augmented insulin pump would have been the correct course of action if she has been experiencing recurrent hypoglycemia, which is not the case.

There is a considerable scope for improvement. She seems to have a degree of insulin resistance and the basal insulin setting is too conservative. Moreover, the excessive rise in glucose in the afternoon and evening is likely due to a combination of low basal insulin rate, inadequate ICR and anerobic exercise. Expected TDD for her weight is 58 units/24 hours (84 [weight in kg] X 0.7), with basal rate being 29 units (50% of TDD), equivalent to 1.2unit/hour. For protection against nocturnal hypoglycemia a 20% lower basal rate (1.0unit/hour) from midnight till 4:00AM is recommended. Moreover, advice on using temporary basal reduction by 50% 1 hour before exercise and for the duration of exercise should be given. Revision of bolus calculator settings should be explored after few days of instituting the basal rate changes.

This patient has been diagnosed with gestational diabetes based on failed values for all time points on her oral glucose tolerance test. Despite a normal HbA1c reflecting her lack of diabetes prior to pregnancy, she has developed GDM at this point in her pregnancy. Her elevated glucose values above pregnancy targets are also confirmed on home glucose monitoring despite already receiving dietary counselling. Overly aggressive dietary counselling is not appropriate as pregnant patients should maintain adequate calorie and carbohydrate intake to sustain the pregnancy and avoid ketosis which can lead to preterm labor. GLP-1 receptor agonist therapy has not been studied in pregnancy and is not a recommended therapy option.

Although metformin and glyburide can be used in pregnancy, opting for insulin therapy is the most likely to be successful at rapidly controlling glucose levels and maintaining glucose control for the duration of the pregnancy in this patient. Tight glycemic control in pregnancy has been correlated with improved maternal and fetal outcomes.

Numerous studies have shown that regular screening and early intervention slow the progression of retinopathy. Only 40% of patients achieve their target HbA1c even two years after starting insulin treatment. Frequent dilated fundus examinations performed by an ophthalmologist serve to assess the degree of retinopathy, educate patients on the potential complications, and reinforce the need for optimal metabolic control. While screening examinations are the cornerstone of managing diabetic retinopathy, this would not be the most appropriate management for this patient.

The patient has proliferative diabetic retinopathy, which can lead to severe vision loss if left untreated. This patient requires treatment for his proliferative retinopathy rather than just on-going screening. Regular screening examinations would be appropriate if the patient had non-proliferative diabetic retinopathy.Panretinal photocoagulation (PRP) is the appropriate management for proliferative diabetic retinopathy. PRP has been shown to reduce the risk of severe vision loss in such patients.

The patient in the clinical vignette above has neovascularization at the disc and in the peripheral retina along with evidence of bleeding (vitreous hemorrhage) from these abnormal vessels. The goal of PRP is to cause regression of neovascularization, and thus, reduce the risk of vision loss. Aggressive metabolic control would help reduce long-term complications in this patient, although it is not likely to have an immediate beneficial effect on retinopathy. Metabolic control is an effective method of slowing the progression of diabetic retinopathy. Intensive metabolic control, as reflected by the HbA1c value, not only reduces the mean risk of developing retinopathy, but also lowers the risk of progression. Stringent goals may reduce long-term diabetes complications, coincident with an increased risk of hypoglycemia, especially in patients with type 1 diabetes mellitus. However, some patients might experience worsening of retinopathy with initiation of aggressive control after years of suboptimally controlled diabetes. In the ACCORD trial, overall mortality was noted to be slightly higher in patients with type 2 diabetes who were randomized to aggressive glycemic control with a target HbA1c less than 6%.

The American Diabetes Association (ADA) recommends individualized HbA1c goals for patients. Young patients with a long life expectancy, low risk of hypoglycemia, and the absence of cardiovascular risk factors can have aggressive HbA1c goals (6%-6.5%), while older patients with a long duration of poorly controlled diabetes and the presence of cardiovascular disease may benefit from less stringent HbA1c goals (7.5%-8%). Also, less-intensive glycemic goals may be indicated in patients with severe or frequent hypoglycemia.Vitrectomy surgery would not be the most appropriate management for proliferative diabetic retinopathy in this patient. Vitrectomy is a surgical procedure that involves removal of the vitreous gel from the eye and relieves areas of vitreo-retinal adhesions. Indications for vitrectomy in diabetic retinopathy include non-clearing vitreous hemorrhage, retinal detachment threatening the macula, and traction on the macula leading to edema.Steroids are potent anti-inflammatory agents that have a role in treating diabetic macular edema but would not be beneficial in the clinical scenario described above. Anti-vascular endothelial growth factor (VEGF) agents also have a role in treating diabetic macular edema, but their role in managing diabetic retinopathy is currently being investigated in clinical trials.

Diabetes is a major cause of cardiovascular disease (CVD), and individuals with chronic kidney disease (CKD) often die of CVD; it is the major cause of death in this patient population. The presence of microalbuminuria, albuminuria, and declining glomerular filtration rate (GFR) are all known predictors of CVD. In the EMPA-REG OUTCOME trial, approximately 7000 subjects were randomized to empagliflozin or placebo and followed for a median of 3.1 years. Those who received empagliflozin had fewer cardiovascular events, defined as the primary outcome (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) compared to placebo (10.5% vs. 12.1%, HR 0.86, 95% CI 0.74-0.99, P=0.04 for superiority).

The rate of hospitalization for heart failure was also lower in the empagliflozin group. Use was associated with a significant reduction in incident or worsening nephropathy (defined as progression to macroalbuminuria, doubling of serum creatinine level, initiation of renal replacement therapy, or death from renal disease) (12.7% vs. 18.8%; HR 0.61, 95% CI 0.53-0.70, P<0.001).  

Diabetic ketoacidosis (DKA) is most commonly reported in patients with type 1 diabetes, but it can also occur in patients with poorly controlled type 2 diabetes in the presence of stress and concomitant medical and surgical illnesses. Drugs that affect carbohydrate metabolism such as corticosteroids, sympathomimetics, and atypical antipsychotics might also precipitate the development of DKA. In recent years, an association between the use of sodium glucose co-transporter 2 (SGLT-2)-inhibitors and DKA has been reported in patients with type 1 and type 2 diabetes.

The US Food and Drug Administration (FDA) and European Medicines Agency have both issued warning statements listing DKA as a rare adverse reaction of SGLT-2-inhibitor treatment. In clinical trials of patients with type 1 diabetes treated with SGLT-2 inhibitors, about 10% of patients developed ketosis and 5-6% required hospitalization for DKA. In patients with type 2 diabetes, DKA is rare, reported in 0.1-0.8 per 1,000 patients. Most cases of DKA occur among patients with a concomitant precipitating cause, such as surgery, alcohol abuse, insulin ­pump mal­function, and poor adherence to medications. Awareness among healthcare professionals, as well as patient education, might facilitate early detection of DKA during SGLT-2 ­inhibitor treatment or even pre­vent development of this diabetes emergency.

Potential strategies include routine monitoring of blood and urine ketone bodies during acute illness, periods of starvation, and in the presence of hyperglycemia. Until more infor­mation is available, the use of SGLT-2 inhibitors should be avoided during severe illness, major surgical procedures, and when ketone bodies are detected despite increases in insulin dose. For patients taking an SGLT-2 inhibitor who present with symptoms suggestive of DKA, such as abdominal pain, nausea, vomiting, fatigue, and dyspnea, a diagnosis of DKA should be considered and an appropriate work-up carried out. Although a low bicarbonate and/or the presence of positive urinary ketones may be suggestive of DKA, these measures may be inaccurate.

Therefore, the American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) recommends direct measurement of blood ketones (beta-hydroxybutyrate) and arterial pH as necessary to confirm the diagnosis. Normal or modestly elevated blood glucose does not exclude the diagnosis of DKA during SGLT-2 inhibitor use. For management of DKA in patients taking SGLT-2 inhibitors, stop the drug immediately and proceed with traditional DKA treatment protocols. Note that although the drug is discontinued, SGLT-2 inhibitor-mediated increases in urinary glucose loss may persist for several days. To minimize the risk of DKA associated with SGLT-2 inhibitors, AACE/ACE recommends stopping the SGLT-2 inhibitor at least 24 hours prior to elective surgery, planned invasive procedures, or anticipated severe stressful physical activity such as running a marathon. Routine measurement of urine ketones is not recommended during use of SGLT-2 inhibitors because this measurement can be misleading. Instead, measurement of blood ketones is preferred for diagnosis of DKA in asymptomatic patients.

Diabetic ketoacidosis (DKA) is the most serious life-threatening hyperglycemic emergency in patients with diabetes. Infections are the most common cause of DKA around the world; however, poor adherence to insulin treatment is the most common precipitating cause of DKA in young patients with type 1 diabetes (T1D) and in inner city populations. Other causes include newly diagnosed diabetes, non-infectious illnesses such as acute myocardial infarction or neurovascular accidents, alcohol use, pancreatitis, and psychological disorders such as depression and eating disorders. Further causes include insulin pump malfunction and certain medications (corticosteroids, sodium glucose co-transporter 2 (SGLT-2)-inhibitors).

The syndrome of DKA consists of the triad of hyperglycemia, ketonemia, and metabolic acidosis. Diagnostic criteria include a blood glucose >250 mg/dL, bicarbonate 12 mmol/L. Although the majority of patients present with plasma glucose levels >250 mg/dL, some patients exhibit only mild elevations in plasma glucose levels. This ‘euglycemic DKA' can be seen during pregnancy, prolonged fasting, or with SGLT-2 inhibitor use.

Treatment goals include correction of dehydration, hyperglycemia, and hyperosmolality, electrolyte imbalance, increased ketonemia, and identification and treatment of precipitating event(s). During treatment, laboratory measurements of glucose and electrolytes, venous pH, bicarbonate, and anion gap should be repeated every 2-4 hours. Intravenous (IV) fluids are a critical aspect of DKA treatment. Treatment with IV fluids alone expands intravascular volume, restores renal perfusion, and reduces insulin resistance by decreasing circulating counter-regulatory hormone levels. Isotonic saline (0.9% NaCL) is the preferred solution and is given at an initial rate of 500-1000 mL/hour during the first 2-4 hours. Most patients with DKA present with a normal or elevated serum potassium level despite a total body potassium deficit. Insulin therapy lowers serum potassium levels by promoting the movement of potas­sium back into the intracellular compartment. Thus, potassium replacement should be started when the serum concentration is This patient presented with severe DKA, hyperglycemia, and hypokalemia. His serum potassium was 3.0 mmol/L. Due to the risk of aggravating the patient's hypokalemia, insulin therapy should be delayed, and the patient should receive IV fluids plus potassium for the first two hours. Serum potassium should be repeated in two hours, and insulin should be delayed until serum potassium is greater than 3.3-3.5 mmol/L.   Option A is incorrect since there is no proven benefit from administering bicarbonate in patients with DKA in the absence of severe metabolic acidosis.

Option B is incorrect since insulin alone without concurrent normal saline and potassium infusion would only worsen hypokalemia and fail to restore circulatory volume for better renal perfusion. Option D is incorrect because half normal saline alone would neither correct hypovolemia nor correct hypokalemia.

It is essential to understand how to convert from multiple daily injections of insulin to a continuous infusion of insulin through an insulin pump. Equations commonly used for determining the basal rates, carbohydrate to insulin ratios, and correctional doses are listed below. These equations are not only useful to determine initial doses of insulin, but can also be useful for long-standing pump users as you review their pump settings and make adjustments based on total doses of insulin and patterns of use.To determine the total daily dose (TDD) of insulin, basal and bolus doses on average should be added together.

To reduce the risk of hypoglycemia, the total dose may be decreased by 20-25% to determine the “pump TDD”. An alternative method suggested by the 2014 American Association of Clinical Endocrinologists (AACE) consensus statement suggests “pump TDD” can be calculated from the patient's weight in kilograms multiplied by 0.5. Both calculations need adjustment based on baseline HbA1c and hypoglycemia history.Calculations for pump settings:1. Basal rate: Pump TDD x 0.5, divided by 24 to determine the hourly rate2. Carbohydrate ratio: 450 divided by pump TDD3. Insulin sensitivity factor: 1700/pump TDDBased on her TDD of 26 units (14 + 12), which would be reduced by 20% (due to her low HbA1c), her TDD would be approximately 20 units per day.20 x 0.5 = 10 divided by 24 hours would be a basal rate of 0.4 units per hour.Carbohydrate ratio would be 450 divided by 20 = 22.5 (rounded up to 25).Sensitivity factor would be 1700/20 = 85.

Rationale: Insulin, produced and secreted by beta cells located in clusters of pancreatic cells called the islets of Langerhans, is the most potent anabolic hormone, promoting the uptake, utilization, and storage of both glucose and lipids. T2DM is characterized by resistance to the actions of insulin in target tissues. Pancreatic beta cells compensate by increasing insulin secretion, and patients with insulin resistance initially have high circulating levels of insulin and maintain normal serum levels of glucose. Eventually, however, pancreatic beta cells start to fail. When they can no longer supply enough insulin to meet these increased requirements, T2DM develops. It is believed that the chronic demand for elevated insulin secretion in insulin resistant subjects unmasks a secondary defect in the beta cells, resulting in progressive loss of beta cell function. Thus, both insulin resistance and insufficiency of beta cell function are important features in T2DM pathogenesis. In addition, glucagon secretion by pancreatic alpha cells appears to be inappropriately elevated in many patients with T2DM, and thus, a decreased insulin:glucagon ratio may also contribute to hyperglycemia in these patients.

Insulin promotes glucose uptake in the fat cell through the translocation of GLUT4 storage vesicles similar to that found in muscle cells. However, the glucose that adipocytes take up is not stored as glycogen, but rather partially metabolized down the glycolytic pathway to form glycerol-3-phosphate. This key metabolic intermediary serves as a backbone to which three FFAs are esterified to form triglyceride, which is then stored in the lipid droplet occupying most of the fat cell. Lipids are delivered to the fat cell through the circulation. Lipoprotein lipase located on the outside of the fat cell cleaves triglycerides to FFAs; these free fatty acids are taken up by adipocytes where they are re-esterified. Insulin enhances adipose tissue lipoprotein lipase expression. Insufficient insulin can contribute to excess levels of circulating FFAs and triglycerides.

The patient has the classic presentation of diabetic amyotrophy. Diabetic amyotrophy (lumbosacral plexopathy, diabetic lumbosacral radiculoplexus neuropathy) presents classically in older type 2 diabetes patients with acute onset, asymmetric, focal pain in one thigh followed by weakness, which then progresses to involve the other leg over the next several months.

Patients with diabetic amyotrophy often have unintentional weight loss and may have autonomic symptoms, with or without associated peripheral neuropathy. This often presents in patients with relatively recent onset diabetes, which is usually in fair control. The exact pathogenesis is unclear, but likely involves ischemia, metabolic, and inflammatory factors. An ischemic nonsystemic vasculitis has been hypothesized as the cause. Electrodiagnostic studies (EDS) reveal markedly reduced amplitudes of sensory nerve and compound muscle action potentials with only mild slowing of nerve conduction velocities.

The risk of hypoglycemia is greatly increased with use of glimepiride and glyburide with an eGFR <60 mL/min/1.73 m2 due to the presence of two active metabolites cleared in part by the kidney. Thus, use of glyburide should be avoided with an eGFR <60 mL/min/1.73 m2.