MODY - It's Not Type 1 and Not Type 2, but Something Else

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MODY - It's Not Type 1 and Not Type 2, but Something Else

Up to 20% of people diagnosed with Type 2 diabetes are not overweight. If you are one of them, it's worth doing some research to make sure that you don't, in fact, have one of the forms of what are often called "Type 1.5" diabetes, forms of diabetes that many doctors do not know about.

There are two major kinds of "Type 1.5." The most common is LADA (Latent Autoimmune Diabetes of Adults) which is a slow-developing form of autoimmune diabetes. Though LADA is usualy considered a form of Type 1 diabetes, research suggests that it may have some genetic overlap with both Type 1 and Type 2 diabetes. You can read more about LADA HERE.

Another, far less common, cause for diabetes in thin people is one of a number of monogenic forms of diabetes which are lumped together under the name MODY. This stands for "Maturity Onset Diabetes of the Young." MODY forms of diabetes are all caused by errors in specific genes. Currently there are twelve forms of MODY that have been identified. Several of these forms of MODY are so rare they have only been diagnosed in one or two families. The most common forms of this rare form of diabetes are MODY-1 and MODY-3, which share several features in common and affect the ability of the beta cell to secrete insulin in response to rising mealtime blood sugars and MODY-2 which affects the "thermostat" used to regulate fasting blood sugar, causing them to remain higher than normal at all times, though mealtime insulin secretion remains normal.

MODY Forms of Diabetes are All Monogenic and Have Little Else in Common

Because each of the identified forms of MODY is caused by a specific defect in one gene most forms of MODY have completely different symptoms from each other. The only thing they all have in common is that they are "monogenic." This means you only need to inherit a single copy of a MODY gene from one parent to develop the related form of diabetes. This is unusual because most genetic diseases require that you inherit the problem gene from both parents to develop the condition.

It is worth noting that though MODY is often called "genetic diabetes" research suggests that almost all forms of Type 2 diabetes are genetic. However, most other forms of genetic Type 2 diabetes are caused by inheriting or acquiring a mixture of damaged genes, not just one, as is the case in MODY. Also, because other genetic forms of diabetes are not monogenic they may require you to inherit a copy of a diabetic genes from both parents.

MODY forms of diabetes were long believed to affect around 2% of all people diagnosed with both type 1 and type 2 diabetes. However, a study of 586 children diagnosed with Type 1 diabetes found that a full 8% of them were actually carrying one of the three most common MODY genes. It is likely that a similar number of people diagnosed with Type 2 may also have one of these genetic forms of diabetes, too. This is because the expression of the gene can vary from mild to severe, so that people with the more common MODY genes may be misdiagnosed with either Type 1 or Type 2 diabetes, depending on the severity of the defect and the age when it is diagnosed.

Prevalence, Characteristics and Clinical Diagnosis of Maturity Onset Diabetes of the Young Due to Mutations in HNF1A, HNF4A, and Glucokinase: Results From the SEARCH for Diabetes in Youth. Catherine Pihoker et al.J Clin End & Metab October 1, 2013 vol. 98 no. 10 4055-4062.

Research Has Changed Our Understanding of MODY

Until the mid 2000s, the MODY form of diabetes were thought to only appear in people under age 25. However, genetic studies where the family members of people diagnosed with MODY were given genetic testing turned up the fact that people carrying the MODY genes are often misdiagnosed as having Type 1 or Type 2 diabetes.

It was also learned that MODY can develop into full-fledged diabetes as late as age 50. The Klupa study, referenced below, found that in one kind of MODY diabetes developed in 65% of those who carried the gene by age 25 years and in 100% by age 50 years, so more than 1/3 of all people with this kind of diabetes do not develop it in youth.

Gene testing also revealed that in some forms of MODY, the blood sugar problems may be so mild as to escape diagnosis.

This study explored the insulin secretion of non-diabetic people carrying one of the more common MODY genes, the gene for MODY-3.

Altered insulin secretory responses to glucose in diabetic and nondiabetic subjects with mutations in the diabetes susceptibility gene MODY3 on chromosome 12 MM Byrne et. alDiabetes, Vol 45, Issue 11 1503-1510

So while it is usually true that a person must have a parent who carries the MODY gene to develop MODY, the fact that neither of your parents was diagnosed with MODY does not rule out the possibility that you have it.

This is especially true if you got your MODY gene from your father. If the MODY gene comes from your mother, it is much more likely that she would have developed gestational diabetes during pregnancy and been diagnosed, though even here you can't be sure as testing and treatment of gestational diabetes in people who were not obese was very lax as recently as the 1980s. But children who are the product of a diabetic pregnancy seem more likely to experience more severe expressions of the MODY genes and hence have worse blood sugars.

Determinants of the Development of Diabetes (Maturity-Onset Diabetes of the Young-3) in Carriers of HNF-1{alpha} Mutations Evidence for parent-of-origin effect Tomasz Klupa, et. al. Diabetes Care 25:2292-2301, 2002

This next study suggests that specific mutations in the gene causing MODY-1 affect the age at which it becomes severe enough to be diagnosed. Different mutations cause different ages of diagnosis.

The Diabetic Phenotype in HNF4A Mutation Carriers Is Moderated By the Expression of HNF4A Isoforms From the P1 Promoter During Fetal Development. Lorna W. Harries et al. Diabetes 57:1745-1752, 2008

The reports I have received from people who have responded to what they learned on this page by requesting testing for MODY forms of diabetes and then discovered they had one of the more common MODY genes suggests that people with MODY often have close relatives a generation older then themselves who were diagnosed with both Type 1 and Type 2 diabetes. These turn out to have the MODY genes too, and point out how commonly these forms of diabetes are misdiagnosed.

Doctors have also discovered that quite a few of the people who were diagnosed with Type 1 diabetes as infants may actually have inherited not one but two copies of a specific MODY gene. This causes a severe form of diabetes usually misdiagnosed as Type 1 diabetes. But since it is actually a genetically caused failure to secrete insulin, people with this disorder can recover the ability to secrete insulin when treated with insulin-stimulating (sulfonylurea) drugs instead of insulin.

Switching from Insulin to Oral Sulfonylureas in Patients with Diabetes Due to Kir6.2 Mutations Ewan R. Pearson, et.al.NEJM. Volume 355:467-477.August 3, 2006, Number 5

People with MODY-3 have been found to have very low Cardiac Specific C-Reactive Protein. (hs-CRP) with the mean of 0.20 mg/l and a range of 0.03 to 1.14 mg/l. This may actually be a cheap and effective screening test for this specific form of MODY as it appears to identify 80% of people with diabetes who actually have MODY. Hs-CRP in people with the other more common form of monogenetic diabetes, MODY 2, have hs-CRP levels very close to that of people with regular Type 2 diabetes.

Assessment of High-Sensitivity C-Reactive Protein Levels as Diagnostic Discriminator of Maturity-Onset Diabetes of the Young Due to HNF1A MutationsKatharine R. Owen, et al. Diabetes Care September 2010 vol. 33 no. 9 1919-1924 doi: 10.2337/dc10-0288

Other Useful References for an Overview of MODY:

Clinical Implications of a Molecular Genetic Classification of Monogenic Beta-cell Diabetes. Medscape CME. Rinki Murphy, MBChB; Sian Ellard, PhD, MRCPath; Andrew T. Hattersley, BMBCh, MA, DM, FRCP.

Molecular and Clinical Characterization of Mutations in Transcription Factors.Timothy M. Frayling, Julie C. Evans, Michael P. Bulman, Ewan Pearson, Lisa Allen, Katharine Owen,
Coralie Bingham, Michael Hannemann, Maggie Shepherd, Sian Ellard, and Andrew T. Hattersley.Diabetes.Vol. 50, Sup 1,Feb 2001

Genetic Types of Diabetes Including MODY (UK - Exeter Research & Testing)

Diagnosis and Management of Maturity-Onset Diabetes of the Young.Timsit, Jose; Bellanne-Chantelot, Christine; Dubois-Laforgue, Daniele Velho, Gilberto. Treatments in Endocrinology. 4(1):9-18, 2005.

Mutations at the BLK locus linked to maturity onset diabetes of the young and -cell dysfunction. Maciej Borowie et al. PNAS, Published online before print August 10, 2009, doi: 10.1073/pnas.0906474106

You can read a slightly more informative report on this study here:

Joslin Study Identifies Gene Linked To Rare Form Of Diabetes

How Do You Get Diagnosed with MODY?

Unfortunately, the only way to get a definitive diagnosis it to take a series of up to 6 expensive genetic tests. But the commonly prescribed tests, from a company called Athena Diagnostics only tests for specific flaws in 6 genees. These tests may be inconclusive since there are a significant percentage of people with clear-cut MODY symptoms and family histories whose MODY is caused by other genes or other flaws in known genes.

A study of individuals with clinically labeled type 2 diabetes, found that when HNF1A and HNF4A were sequenced in 80 subjects with diabetes, who were diagnosed younger than 30 years or and/or who were diagnosed with diabetes younger than 45 years old who didn't have metabolic syndrome, 12 of the subjects were found to have mutations in the HNF1A and HNF4A genes suggestive of MODY. This represents 15% of those 80 subjects. Most significantly, though, of these 12 subjects, only 47% of MODY subjects identified met current guidelines for diagnostic sequencing. This means that if they took the standard MODY tests their mutation would not have been found.

The study concludes, "We recommend that all patients diagnosed before age 30 and with presence of C-peptide at 3 years' duration [be] considered for molecular diagnostic analysis." Note that this is not the same as taking Athena Lab's MODY tests but involves looking directly at the MODY genes for evidence of any significant defect.

Systematic Assessment of Etiology in Adults With a Clinical Diagnosis of Young-Onset Type 2 Diabetes Is a Successful Strategy for Identifying Maturity-Onset Diabetes of the Young. Gaya Thanabalasingham et al. Diabetes Care Diabetes Care June 2012 vol. 35 no. 6 1206-1212

The Joslin Diabetes Center web site states that one third of the families with the symptoms of MODY diabetes that they are following do not have a form of diabetes that can be diagnosed as one of the six forms of MODY already identified.

Even worse, most health insurers will not automatically pay for these genetic tests. So if you are a thin person with adult-onset diabetes you may have to approach a diagnosis by ruling out autoimmune diabetes (LADA), looking at your family history, your personal history, your weight history, and at indications of how insulin resistant you are.

Some factors that might suggest that you possibly have MODY

Before your read the following, be aware that MODY forms of diabetes are rare. Very few people diagnosed with Type 2, including many who are of normal weight, will turn out to have MODY. The list that follows lays out some factors that might suggest that more detailed testing is worthwhile. The symptoms listed may point to one of the more common forms of MODY, each one of which has different symptoms.
  • If you are diagnosed with diabetes through you have always been of a normal or near normal weight or were at a normal weight until shortly before your diabetes diagnosis. (However, be aware that in some forms of MODY the high blood sugars can cause mild insulin resistance which can lead to weight gain.).
  • If your High Sensitivity (cardiac specific) C-Reactive Protein is low, ranging from 0.03 to 1.14 mg/l, but tending towards the lower end of this range. This is a characteristic of MODY-3.

  • If you have a history of gestational diabetes that occurred when you were at a normal weight and which developed very early in the course of the pregnancy. In people without MODY or LADA, gestational diabetes typically develops only in the last trimester. With MODY-1 and -3 it can develop only a few months into the pregnancy. The high blood sugars may also increase insulin resistance and cause sudden, dramatic, otherwise inexplicable weight gain.
  • If you have close relatives who had adult onset diabetes who were of normal weight.
  • If taking a drug that improves insulin resistance like Metformin doesn't make a significant change to your A1c but you don't have any evidence of autoimmune diabetes.
  • If you have glucose in your urine though your doctor tells you you are not diabetic, especially if there is a history of kidney disease in your family. MODY-3 causes glucose to be excreted in the urine at abnormally low blood sugar levels.
  • If you have an very elevated fasting blood sugar--over 125 mg/dl that cannot be lowered with diet, drugs of insulin. (This is characteristic of MODY-2)
  • If you have several relatives diagnosed with both Type 1 and Type 2 diabetes, none of whom is obese.

What are the Characteristics of MODY Diabetes?

First of all, it's important to remembers that the forms of diabetes classed as MODY are all different and unrelated to each other. Each has different characteristics. The ADA "Expert's Committee Report on the Criteria for the Diagnosis of Diabetes Mellitus", which was published in 1998, reports there were three such mutations known. Today a web search will turn up the information that there are 11 known genetic flaws labeled as MODY. A researcher from the Joslin Diabetes Clinic told me in 2008 that they were at the time doing a study of families with possible MODY to identify new MODY genes and that they expected to find dozens of them.

There are differences between how the different versions of MODY manifest. But here are some of the traits several forms of MODY have in common:

  • People with MODY are usually of normal weight, at least until shortly before their diabetes diagnosis. This is also true of people with LADA . However, people with MODY do not have the GAD or islet antibodies characteristic of people with LADA, which unlike all forms of MODY is an autoimmune disease.
  • People with one of the forms of MODY that primarily affect the secretion of insulin in response to a meal may have near-normal fasting blood sugar test readings and very high post-meal blood sugars. This can result in them maintaining an A1c below 7.0% which most doctors will ignore. But decades of exposure to these higher than normal post-meal blood sugars can cause complications, especially heart disease.
  • The age of onset of diabetes in at least one form of MODY depends on the parent who passed on the mutant allele. It is significantly younger if it was the mother who passed on the gene and if she had diabetes during the pregnancy. That may be because exposure to high blood sugars in the womb affects the expression of the MODY gene in the offspring. If you have been diagnosed with gestational diabetes when not overweight and your child develops pre-diabetes or diabetes by her 20s without obesity, MODY may be a possibility.
  • MODY may develop at any age up to 55. Unfortunately, many documents about MODY repeat the outdated information that MODY only strikes people under 25, and many doctors continue to believe this. More recent research has shown this is not true, especially for people with milder, harder to diagnose, versions of MODY.
  • Mothers with MODY are often diagnosed only after a child develops diabetes. They almost always develop gestational diabetes very early in their pregnancies, but obsteticians rarely test for MODY. Pediatric endocrinologists who are more aware of MODY than endocrinologists who treat adults appear to be testing children for MODY more frequently than they did in the past. Often, only when a child is found to have a form of MODY, will the parents be tested.
  • People with some forms of MODY are not insulin resistant. They will respond to very small doses of insulin or drugs that stimulate insulin production. If misdiagnosed as having Type 1 diabetes and given insulin, they will typically remain using the very low doses used in the so-called "honeymoon" stage of Type 1 diabetes. However, this is not always true of other forms of MODY where high blood sugars apparently cause insulin resistance, though the genetic defect, not the insulin resistance, is thought to be the primary cause of the diabetes.
  • MODY-1 and MODY-3 respond very well to drugs that stimulate insulin secretion. In these forms of MODY, the genetic defect causes the beta cell to fail to get the signal telling it to secrete insulin when blood sugar starts to rise. A strong response to a very small dose of a sulfonylurea drug or repaglinide may actually be diagnostic of the two forms of MODY that have this characteristic.
  • In one common form of MODY, fasting blood sugar is normal, but insulin secretion begins to fail as blood sugars go over 144 mg/dl. This can lead to a difficult to diagnose form of diabetes as fasting blood sugar may remain normal for many years.

  • People with another common form of MODY, MODY-2, have a defect is in the production of Glucokinase which acts as a "thermostat" for fasting blood sugar levels. They have elevated fasting blood sugars (125-140 mg/dl) which cannot be lowered, however this form of diabetes rarely progresses and can be controlled with diet. It is usually described as rarely causing the severe complications of other forms, though I have received anecdotal reports from people whose families carry this gene that fatal heart attacks in the 50s are common--a very significant diabetic complication!.

  • In several forms of MODY (MODY-3 and MODY-5 people may spill glucose into their urine at very low blood sugar levels--140 mg/dl(7.8 mmol/L) or less. People with these forms of MODY often have subtle or obvious congenital kidney defects and may even have signs of kidney disease before they are diagnosed with diabetes.

You can read of a typical example of how MODY is misdiagnosed in this journal article that describes a family where a father is misdiagnosed as having type 2 and his daughter as having type 1. After genetic testing, both turned out to have MODY-1.(HNF4-a Gene)

Identification of MODY:The implications for Holly. Journal of Diabetes Nursing, Jan, 2004 by Jo Dalton, Maggie Shepherd

Indications You Do NOT Have MODY

Because I have been getting a lot of email from site visitors who seem to hope they have MODY as it sounds more interesting than plain old garden variety Type 1 diabetes, though they don't have any of the symptoms that would suggest any form of MODY diabetes, it's important to list the symptoms that would make it unlikely that you have any form of MODY.
  • Low fasting insulin or c-peptide level. People with several of the more common forms of MODY usually have normal or near normal fasting insulin levels. The genetic defects they have primarily affect post-meal insulin secretion. A low fasting insulin or C-peptide is much more likely to point to LADA. Read about LADA HERE. LADA is much more common than MODY and the most frequent cause for abnormal blood sugars in thin people who have been misdiagnosed with Type 2 diabetes.

  • GAD or Islet Antibodies or Diagnosis of Other Autoimmune Disease Anyone who tests positive for autoimmune disese is much more likely to have a form of autoimmune Diabetes, either Type 1 or LADA.

  • Sudden onset of abnormal blood sugars that deteriorate swiftly. People with MODY are born with MODY and will have slightly abnormal post-meal blood sugars or fasting blood sugar levels, all their lives, though they may be too low to be caught by any of the tests used to screen for diabetes. Blood sugars may become worse with increasing age but in general the progress is gradual. The sudden onset of abnormal blood sugar or a blood sugar that deteriorates dramatically over a brief period is more likely to point to LADA.

  • Use of normal Type 1 insulin doses. If you are using a typical Type 1 dose of insulin, you aren't likely to have MODY. People with MODY typically use the very small insulin doses used during the Type 1 "honeymoon" period all their lives. A typical Total Daily Dose for a person with MODY may be 10 to 20 units depending on body size. In addition, because there is often intact basal insulin secretion, a person with MODY may need much more meal-time insulin than basal insulin.

  • Use of normal Type 2 insulin doses People with MODY are insulin sensitive--often highly insulin sensitive. If you are using over 10 units a day of basal insulin or injecting more than 5 or 6 units at meal time you are very unlikely to have one of the commoner forms of MODY.

  • Normal Responses to Type 2 Drugs People with MODY rarely see any significant effect from drugs that lower insulin resistance. At the same time, they have a dramatic response to very low doses of drugs that stimulate insulin secretion like sulfonylurea drugs (glipizide, glimipiride, glyburide etc.) or repaglinide (Prandin). If you can take a normal dose of a drug like glyburide or glibenclamide without hypoing, you aren't likely to have one of these forms of MODY. People with MODY are likely to respond to 1/4 of the lowest dose available very strongly.

What if You Do Have MODY?

  • Most forms of MODY are very like Type 2 diabetes in their effect on your body. Elevated blood sugars injure you slowly over many years. So if you don't learn how to control your post-meal blood sugars effectively these elevated sugars will eventually cause neuropathy, retinopathy, heart disease and the other ugly complications of diabetes.
  • The recommended treatment for MODY depends on the severity of the diabetes. Some people with MODY can maintain normal blood sugar levels by restricting carbohydrates. The Glucokinase version of MODY is the one most amenable to dietary control. Please note that doctors often tell people that it is not possible to lower the high fasting blood sugars found in MODY-2 using carbohydrate restriction, but I have heard from people who have been given diagnoses based on genetic testing who found that carb restriction at meal time did lower their fasting blood sugar to safer, if not completely normal, levels.

    Others with MODY-1 or MODY-1 may be treated with very low doses of drugs that stimulate insulin secretion. Dr. Andrew Hattersley, the MODY expert who has published the most about MODY, recommends very low doses of Gliclazide (Diamicron), a mild, heart-safe sulfonylurea that is not available in the United States.

    The related sulfonylurea drugs that are available in the U.S. are Amaryl and Glipizide though some people with MODY report these drugs are too powerful. In addition, the sulfonylurea drugs available in the U.S. have been found to raise the potential for heart attacks.

    Alternatives are the newer "glinide" drugs, such as repaglinide (brand name Prandin) Prandin is heart-safe and lasts for only a few hours after a meal, making it less likely though far from impossible that the drug will cause hypos,

    Others with MODY-1 and -3 prefer to use injected insulin. Doctors assume you'd prefer a pill to shots, so they often suggest the oral drugs that stimulate insulin secretion rather than insulin. But the side effects of all the insulin-stimulating drugs, can be a problem. They may cause relentless hunger and weight gain and they may possibly raise the risk of heart attack. Sulfonylurea drugs also tend to cause hypos at doses high enough to give near-normal blood sugars.

  • Many people with MODY diabetes report that insulin gives them better control and is less likely to cause hypos at doses that give tight blood sugar control. Used in the tiny doses characteristic of MODY insulin won't usually cause weight gain. However, there is another school of thought that believes it is better to stimulate insulin secretion in the beta cell, if possible, rather than inject synthetic forms of insulin because insulin produced by our own beta cells is produced along with a substance called C-peptide.

    C-peptide was long believed to be inert, but much recent research has found that, in fact, C-peptide plays an important part in preventing vascular complications. Injecting insulin may shut down native insulin production, so a person with MODY who injects insulin might therefore end up with less C-peptide, which might make them more prone to develop microvascular complications.

    This may be the reason that the MODY expert Dr. Hattersley recommends the use of sulfonylureas rather than insulin for people with MODY-1 and MODY-3.

    Fasting Plasma C-Peptide and Micro- and Macrovascular Complications in a Large Clinic-Based Cohort of Type 1 Diabetic Patients
    Francesco Panero et al, Diabetes Care February 2009 vol. 32 no. 2 301-305

    Insights into the Beta-cell from patients with monogenic diabetes. Andrew Hattersley. EASD lecture, Sept 15, 2015. http://www.easdvirtualmeeting.org/resources/insights-into-the-beta-cell-from-patients-with-monogenic-diabetes

    Unfortunately, the specific sulfonylurea drug he recommends, Gliclazide (Diamicron) is not available in the U.S..

    If you can get good control with an oral drug it might be worth pursuing, but if you cannot get normal blood sugar readings any advantage you get from manufacturing C-peptide might be outweighed by the damage done by high blood sugars.

    The newer incretin drugs, Byetta and Januvia also produces normal or near normal blood sugars for some people with forms of MODY that respond to beta cell stimulation. But these drugs'potential to promote cancer and pancreatitis should rule them out.

  • If you suspect you have MODY and your doctor wants you to start insulin, a sulfonylurea drug, or a drug like Prandin, be sure to start at a very low dose. The starting dose of either a sulfonylurea drug or insulin that is appropriate for a person who is an insulin resistant Type 2 may be anywhere from two to ten times higher than the dose that works well for a person with MODY. So a typical type 2 dose may cause dramatic hypos.

    The recommended starting dose for glimepiride (Amaryl) for someone with MODY, for example, was .25 mg, but since this doesn't adjust for body size, if you are small, even this dose may be way too much. With meal-time insulin, start with 1 unit and work up to the dose that gives you good control for a given number of grams of carbohydrate. Many people with MODY-1, -2, or -3 may do well with as little as 2-5 units a meal. If prescribed a basal insulin like Lantus, start with 2 or 3 units and work up, as the starting doses prescribed for people with Type 2 may be fare too powerful and cause hypos.
  • If you suspect you have MODY diabetes and are of childbearing age, and if there is diabetes in your spouse's family, consider genetic testing. Though it is very rare to have two copies of the same MODY gene, a child who inherits two copies of the same MODY gene will be born with a severe form of diabetes.

The Complications Seen With MODY Vary But Tight Blood Sugar Control is Always Essential

High blood sugars damage your organs no matter what kind of diabetes you have. So you will still want to strive for Healthy Blood Sugar Targets. The more normal your blood sugars, the less likely you are to develop complications, no matter what gene is causing your abnormal blood sugars.

Even in families that carry "Mild" versions of MODY genes, while there is often no history of retinopathy or kidney failure, there may be a family history of a much higher incidence of fatal heart attacks in people in their fifties. This is because heart attack risk rises with even modestly elevated post-meal blood sugars and people with "mild" forms of MODY have these elevated post-meal blood sugars all their lives. You can learn more about this connection here: Elevated Post-Meal Blood Sugars and A1C Predict Heart Attack. If your doctor is not willing to work with you to help you achieve safe blood sugar levels, look for a doctor who will be more supportive.

The gene defects that cause MODY-3 and MODY-5 also may cause congenital kidney problems that are not the same as the kidney problems caused by high blood sugars. If you are diagnosed with either of these kinds of MODY, you must insist on seeing a highly qualified kidney specialist who can help you learn the best preventative treatments for the specific kidney malformation you might have.

Do You Need MODY Testing?

Right now, MODY testing is extremely expensive and may not be covered by your insurance. Each gene tested for may cost up to $500, but experts on MODY say there are probably dozens more MODY genes we don't yet know about so you may have all the symptoms of a form of MODY diabetes but still have your tests come up negative.

It is also possible that there are non-monogenic forms of diabetes that have the same symptoms as MODY diabetes that are caused by recessive genes that damage the same genes involved in MODY. These genes may not show up in standard MODY testing.

If you are considering getting this testing and must pay for it yourself, ask yourself, "What changes would a positive test make in my treatment plan?" For many of us, the answer is, "none." If this is the case for you, there is no immediate reason to pursue testing.

Special Concerns for People with MODY-2

Some people diagnosed with MODY-2 find it does not require any treatment beyond carb restriction. However, some people who have this gene find they need insulin to control their post-meal numbers. Unfortunately, doctors have recently been told, based, as usual, on misinterpretation of some studies--that there is no need at all to treat MODY-2 at all. This is because the studies found that people with MODY-2 don't develop the classic diabetes complications of neuropathy, retinopathy, and kidney disease. Unfortunately, this ignores the fact that people with MODY-2 do develop heart disease, which is caused by prolonged exposure to blood sugars that rise to levels much lower than those that cause the classic complications. Because of this mistaken belief, people who have had their diabetes well controlled with insulin have had their insulin prescriptions cancelled upon receiving a diagnose of MODY-2 due to genetic testing. If you suspect you have MODY-2 but have your diabetes well under control with insulin, it might be wise to avoid getting a diagnosis that will take away your insulin. If you have a diagnosis already and can't get any drug help from doctors, lowering your post-meal blood sugars with the strategy described HERE should help you prevent this from happening to you.

Considerations with MODY-3 and MODY-1

The other two most common forms of MODY, it has been found that sulfonylurea drugs and the "glinide" drugs like repaglinide may be effective in controlling blood sugars. This means you if you are currently on insulin but are diagnosed with one of these MODYs, you could take these pills instead of shots.

Doctors often think this is what patients would like, but my own experience and that of several other people with MODY-1 and MODY-3 who have contacted me is that these sulfonylurea drugs, while very effective at lowering blood sugar at very low dosages, produce constant, gnawing hunger, which makes them unpleasant to take. Small doses of insulin, in contrast, control blood sugars equally well without the hunger side effect. In addition, insulin can be matched to incoming food, while the pills cause an unregulated release of insulin which forces you to eat to keep up with the insulin.

If you are already controlling your diabetes on small doses of insulin, and don't want to change, then testing for MODY might be a bad idea, as a MODY diagnosis might result in your pump or insulin prescription being taken away and replaced with a prescription for the far cheaper insulin-stimulating pills which may give you poorer control. This could be a disaster.

However, if you meet some of the criteria for potentially having a form of MODY and are not happy taking insulin,you might ask your doctor for a brief, supervised trial of glimepiride or repaglinide using the dosing data published by the Royal Devon and Exeter hospital pm this page:
Guidance for transferring HNF1a or HNF4a patients from insulin to sulfonylureas


There is contact information on The Royal Devon and Exeter Hospital web site which will allow your doctor to discuss this with professionals who have published extensively on this subject. This site also provides genetic testing. It is not-for-profit, unlike the other sites offering MODY testing, and I have heard reports of good experiences with their service.

The other reason you might want a MODY diagnosis is if you are normal weight with an A1c your doctor considers good (high 5% to 6.5%) but find it impossible to keep your post-meal blood sugars near normal. Because MODY-1 and MODY-3 mainly effect post-meal blood sugars people with milder forms of these MODYs may have trouble getting the treatment they need, which may be s small dose of insulin at meals.

More severe forms of MODY-1, MODY-3 and MODY-5 may be indistinguishable from Type 1 and people with them may do very well on insulin pumps.

Finally, if you and your child are both diagnosed with diabetes and the rest of your family history is suggestive of MODY you should ask for gene testing because a diagnosis of a form of MODY that responds to pills might allow for more flexibility in treatment for your child. Plus a positive MODY test result will give an informed doctor a better understanding of what are otherwise confusing responses to insulin.

The Renal Threshold Test for MODY-3

There is one useful home test you can do on your own that can help you determine if you may have MODY-3, the most common form of MODY, which affects the HNF1-a transcription factor.

People with MODY-3 usually have an abnormally low renal threshold for glucose. This means that they will spill glucose into urine at abnormally low levels. A normal renal threshold is usually found when blood sugar reaches around 180 mg/dl. However, people with MODY-3 may find glucose in their urine when blood sugar is at 140 mg/dl.

You can test your own renal threshold using glucose urine test strips which you can buy at any pharmacy for about US$10. Test 2 or 3 hours after eating. If you see glucose in your urine when your blood sugar has risen no higher than 150 mg/dl at any time after your previous meal, and have other symptoms of MODY discussed above, the low urinary threshold for glucose raises the likelihood that you do, in fact, have MODY-3.

People with MODY-3 are more likely to develop kidney disease, so if you find a low renal threshold, you will want to pursue extremely tight blood sugar control--keeping blood sugars below your renal thresholds as much as possible, and should demand that your doctor does the microalbumin test every year.

Insulin Sensitive Type 2 Diabetes

There is another possibility to consider if you have many of the symptoms described above. There are other, not yet identified. genetic defects besides the ones that are defined as MODY that cause insulin sensitive forms of Type 2 diabetes. These may not be monogenic so you would have inherited a relevant gene from both your parents. Though the genetic determinant may be different from those causing MODY, the clinical manifestations may be the same: high blood sugars along with a lack of obesity, the development of gestational diabetes at a normal weight, and normal or high sensitivity to injected insulin. The treatment options for these kinds of Type 2 diabetes are similar to the treatment options for MODY. Low dose insulin after meals or insulin stimulating drugs at low doses

If You Think You Have MODY - Join Our Data Collection Effort


The mail that I've been getting from readers of this page suggests there are many more people with MODY out there than doctors realize, probably because so many of us get misdiagnosed.

If you'd like to join the effort to collect and share more information about people with diagnosed or suspected MODY please EMAIL us with information about your own experience with MODY diabetes.

There are currently no studies I can refer you to, but your experiences, especially if they don't match what your doctors have told you, may be useful to other people who contact me. Since this page is one of the more visible resources for people with MODY, I do hear from them from time to time.

Please note that if you are not of a Western European ethnicity, it is quite possible that you have a form of MODY that has not yet been discovered. I hear from quite a few slim Asians and people from the Middle East who have insulin sensitive forms of diabetes without autoimmune antibodies that don't test positive on any of the currently available MODY gene tests.





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