1300 Units Insulin Daily: A Rare Case of Insulin Resistance Syndrome in a Woman

Insulin resistance is the primary reason adults develop Type 2 Diabetes. The most common causes of insulin resistance are:

• Metabolic Syndrome
• Acquired Insulin resistance syndromes due to inactivity, obesity, chronic inflammation, and intake of high fat, high sugar diet.
• Gestational diabetes (due to placental hormones)
• PCOS (Polycystic ovarian syndrome)

All these medical conditions require medications to counteract insulin resistance, enhance insulin sensitivity, and sometimes exogenous insulin.

If required, insulin dose does not exceed 1 – 2 units per kg in the majority of the patients. Most patients require less than 100 units of insulin daily.

Some patients require very high doses of insulin, exceeding more than 2 units per kg. These patients may have any of these rare types of insulin resistance syndromes:

1. Type A Insulin Resistance Syndrome

• Description: A rare genetic condition often seen in young women, characterized by severe insulin resistance despite normal body weight.
• Associated Features:
  • Hyperandrogenism (high male hormone levels)
  • Polycystic ovary syndrome (PCOS)-like features
  • Acanthosis nigricans (dark patches of skin)
  • Virilization in extreme cases

2. Type B Insulin Resistance Syndrome

• Description: An autoimmune disorder where the body produces antibodies against the insulin receptor.
• Associated Features:
  • Occurs mostly in middle-aged women
  • May be associated with other autoimmune diseases like lupus
  • Severe insulin resistance that develops suddenly
  • Acanthosis nigricans and hyperandrogenism may also be present

3. Lipoatrophic Diabetes

• Description: A group of disorders characterized by a loss of subcutaneous fat, leading to severe insulin resistance.
• Associated Features:
  • Partial or total loss of body fat (lipodystrophy)
  • Hypertriglyceridemia (high blood fats)
  • Hepatomegaly (enlarged liver)
  • Acanthosis nigricans

4. Familial Partial Lipodystrophy (FPLD)

• Description: A genetic disorder where fat distribution is abnormal, leading to insulin resistance.
• Associated Features:
  • Loss of fat in the limbs and trunk with fat accumulation in other areas (e.g., face, neck)
  • Hypertriglyceridemia
  • Hepatic steatosis (fatty liver)

5. Donohue Syndrome (Leprechaunism)

• Description: A rare, severe form of congenital insulin resistance.
• Associated Features:
  • Extreme insulin resistance from birth
  • Growth retardation
  • Characteristic facial features (small stature, elfin appearance)
  • Early death, usually within the first two years of life

6. Rabson-Mendenhall Syndrome

• Description: A rare inherited form of insulin resistance.
• Associated Features:
  • Severe insulin resistance in childhood
  • Growth abnormalities
  • Early onset diabetes
  • Acanthosis nigricans and dental abnormalities

1300 Units of Insulin Per Day: A Woman with Severe Insulin Resistance and Weight Loss

This case report was published in the NEJM. The case is about a 46 years of age woman with the diagnosis of type 2 diabetes which was refractory to insulin therapy.

The woman was labeled as Type 2 Diabetic 5 years back. At that time she weighed 113 kg (249 lbs) and had a BMI of 45.6 kg/m2.

At that time she was started on Insulin Glargine and metformin, however, due to metformin intolerance, she was then switched to Glipizide.

Over the next 3 years, her glycemic control worsened and she lost 50 kg of her baseline body weight. She weighed 63 kg and had a BMI of 25.4 kg/m2.

Her A1C was 13.2% and she was on 20 units of glargine and Glipizide. She was given a trial of Jardiance but it was stopped because she developed a urinary tract infection.

The patient was switched to Insulin Lispro 30 units per day along with Insulin Glargine 30 units, Glimepiride and Pioglitazone.

When she was seen one year after, her A1C was 14% and she weighed 48 kg. She had lost another 14 kg weight over the last year. Her BMI was 19.4 kg/m2 then.

Her weight dropped further and glycemic control worsened over the next few months.

She developed abdominal pain and was investigated for DKA (diabetic ketoacidosis) and HHS (Hyperosmolar Hyperglycemic state) which were ruled out.

A presumptive diagnosis of lipodystrophy was made and she was started on 250 units of human regular insulin in the morning and 200 units with lunch and dinner.

At the same time, she was tested for autoimmune diabetes but her antibodies to glutamic acid decarboxylase, islet antigen 2, and zinc transporter 8 were all negative.

During the next two months, the patient had multiple hospitalizations for severe hyperglycemia and abdominal pain.

She also had an upper GI endoscopy done and was treated for H.Pylori infection associated with erosive gastritis.

During the current admission, she had marked weight loss. Her BMI this time was 17 and she looked cachectic. She also had an acromegalic look.

She had numerous skin tags, acanthosis nigricans, vitiligo, and skin breakdown in the legs. Abdomen was diffusely tender but there was not visceral enlargement.

Her laboratory workup included:

Because the patient had normal triglyceride levels, normal adiponectin levels, and normal SHBG, she was given the diagnosis of Type B Insulin Resistance Syndrome (and not lipodystrophy).

The patient was started on immunotherapy. She started gaining weight, her A1C dropped by 2.4%, however, she had complications related to immunosuppression.

She is being continued on high-dose insulin with the goal of complete remission over time and monitoring for infections and other complications of immunotherapy.

Final Remarks:

This is a very unusual case of a woman requiring almost 40 units per kg of insulin per day. Most diabetics require fewer than 1 to 2 units per kg of insulin daily.

In addition, despite losing weight, her insulin requirements were progressively increasing. On the contrary, she was not developing acute complications of diabetes like DKA and HHS.

Other similar conditions include rare hereditary disorders, as previously mentioned. In patients with both insulin and glucagon deficiency—such as those with combined exocrine and endocrine pancreatic insufficiency—blood sugar levels remain highly uncontrolled, yet the patient does not develop DKA (diabetic ketoacidosis) or HHS (hyperosmolar hyperglycemic state).

A notable example of this is tropical diabetes, also known as malnutrition-related diabetes (MRDM). However, insulin requirements are way less than that seen in this patient.