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By Dr. Liji Thomas, MD Jul 25 2023 Reviewed by Danielle Ellis, B.Sc.

Type 2 diabetes melllitus (T2DM) is a common disease, the prevalence of which is increasing exponentially. It is estimated that by 2030, almost 440 million adults below the age of 80 will have diabetes. The consequences of T2DM on health and mortality have long been a focus of study. However, the medications used to control this dreaded disease have their effects on the body, causing specific adverse effects. Study: Diabetes medications and cancer risk associations: a systematic review and meta-analysis of evidence over the past 10 years. Image Credit: fizkes/Shutterstock.com

Cancer is found to occur at higher rates in people with diabetes, probably because both are associated with common risk factors. Diabetes drugs may also contribute to the risk of cancer.

In an attempt to discern the risk of cancer posed by certain diabetic drugs as well, the authors of a recent paper performed a systematic review and meta-analysis of all studies over the past ten years dealing with this topic. The research was published in Scientific Reports. Introduction

Cancer risk factors among people with diabetes include smoking, lack of physical exercise, overweight, and poor dietary quality. These reflect a state of inflammation, high blood sugar levels, and excessive amounts of insulin in the blood. Several studies have also shown that certain cancers occur more often among those who use specific diabetes drug categories.

The current review aimed to bring together the risk of multiple cancer types at various sites with the different types of medication used to treat diabetes. Earlier studies have looked mostly at how one class of medication affects cancer risk at different sites or, conversely, how all diabetes drugs affect cancer risk overall. The main focus remained on cancers of the breast, lung, liver, and pancreas, as well as CRCs.

The various drug classes explored were biguanides, those based on incretins, alpha-glucosidase inhibitors (AGIs), insulin secretagogues, thiazolidinediones, and insulins. What did the study show?

The review included 92 studies, of which three were randomized controlled trials (RCTs), while the majority (64) were cohort studies. The remaining comprised case-control studies. All three RCTs suffered from poor design, leading to a high risk of bias. Related StoriesUSC study reveals key details about how cancer cells metastasizeUnderstanding the impact of HPV on the vaginal microbiome and its role in cervical cancerWhat is the relative burden of oncologic and nononcologic mortality among long-term survivors of cancer in the US?

The cohort studies were mostly at low risk of bias, as were the case-control studies. The most studied cancers were CRCs and pancreatic cancers. Breast and lung cancers were mostly studied in cohort studies. Lung and liver cancers, and CRCs, were studied in both Asian and Western regions, whereas most research on breast, prostate, and pancreatic cancer was carried out in Western populations.

The results showed that colorectal cancer (CRC) and liver cancer occurred at lower rates among diabetic patients who used biguanides to control their blood sugar levels. The risk of liver cancer was reduced by an impressive 45% and that of CRC by 15%. In case-control studies alone, biguanide use was linked to an increase in pancreatic cancer odds by 25%.

Biguanides regulate energy and cellular metabolism, reducing the levels of oxidative stress, inflammation, and apoptosis, along with reduced body fat formation.

Similarly, breast cancer and liver cancer risk were reduced by about 15% with thiazolidinedione use, while the odds of lung cancer were lowered by 44%. These medications reduce the rates of breast cancer cell division and promote apoptosis while restricting neovascularization of tumors. In the liver, these agents cause the protein p27Kip1 to accumulate, limiting liver cell growth and, thus, perhaps, preventing cancerous changes.

Insulin use was linked to a 25% reduction in the odds of prostate cancer and a 10% drop in breast cancer odds. However, insulins were associated with massive increases in the risk of two cancers; pancreatic cancer risk went up by 240%, while there was a 74% increase in the risk of liver cancer.

The raised liver cancer risk was only among Western populations using insulin, with an increase of 250% in this subgroup. Insulin-resistant patients have high insulin levels in the portal circulation, which reaches the liver, and this might account for some of the risks.

Pancreatic cancers might form or grow faster when exposed to insulin, which promotes growth and cell division. However, severe diabetes is itself a risk factor of pancreatic cancer, adding a confounding factor to the etiology.

With insulin secretagogues, the risk of pancreatic cancer went up by 26%. Cohort studies, but not case-control series, showed a 20% rise in associated CRC following insulin secretagogue use. These agents promote insulin secretion by the pancreas, thus raising insulin-like growth factor 1 levels. Enhancing the rate of cell division may promote pancreatic cancer. What are the implications?

Overall, biguanide and thiazolidinedione use carried no risk, or potentially lower risk of some cancers, while insulin secretagogue and insulin use were associated with increased pancreatic cancer risk.”

The benefits of several medications used to treat diabetes extend to a reduction in the associated risk of cancer. At the same time, the risk of pancreatic and liver cancer shot up in association with the use of insulin and of pancreatic cancer with insulin secretagogues, though to a much lesser extent.

While showing associations between medication classes and cancer risk, the study also emphasizes regional differences as well as discrepancies between different study designs. Other confounding factors may have been at work, such as differences in nutritional status.

These findings suggest that it may be important to weigh the potential harms of insulin among patients with diabetes who are at high risk of liver or pancreatic cancers due to family history or other risk factors.” Journal reference: Chen, Y. et al. (2023) "Diabetes medications and cancer risk associations: a systematic review and meta-analysis of evidence over the past 10 years", Scientific Reports, 13(1). doi: 10.1038/s41598-023-38431-z. https://www.nature.com/articles/s41598-023-38431-z

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Kemi Badenoch does not rule out local coalitions with Reform after next week’s council elections

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Kemi Badenoch does not rule out local coalitions with Reform after next week's council elections

Kemi Badenoch has not ruled out forming coalitions at a local level with Reform after the council elections next week.

Speaking to Sunday Morning with Trevor Phillips, the Conservative leader did however categorically rule out a pact with Nigel Farage’s party on a national level.

“I am not going into any coalition with Nigel Farage… read my lips,” she said.

However, she did not deny that deals could be struck with Reform at a local level, arguing that some councils might be under no overall control and in that case, “you have to do what is right for your local area”.

“You look at the moment, we are in coalition with Liberal Democrats, with independents,” she said. “We’ve been in coalition with Labour before at local government level.

“They [councillors] have to look at who the people are that they’re going into coalition with and see how they can deliver for local people.”

She added: “What I don’t want to hear is talks of stitch-ups or people planning things before the results are out. They have to do what is right for their communities.”

More on Electoral Dysfunction

A total of 23 councils are up for grabs when voters go to the polls on Thursday 1 May – mostly in places that were once deemed Tory shires, until last year’s general election.

It includes 14 county councils, all but two of which have been Conservative-controlled, as well as eight unitary authorities, all but one of which are Tory.

Ms Badenoch has set expectations low for the Tories, suggesting they could lose all the councils they are contesting.

The last time this set of councils were up for election was in 2021, when the Conservative Party was led by Boris Johnson who was riding high from the COVID vaccine bounce.

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Landeskog scores 1st NHL goal in nearly 3 years

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Landeskog scores 1st NHL goal in nearly 3 years

Perhaps the only detail more emphatic than the goals in the Colorado Avalanche‘s 4-0 win over the Dallas Stars Saturday night, was the impact provided by their captain, Gabriel Landeskog.

Landeskog, who returned in Game 3 of this Western Conference first-round series after missing nearly three seasons while recovering from a knee injury, scored his first goal since June 20, 2022, in a multi-point performance that saw the Avalanche tie the series at 2-2 in Game 4 at Ball Arena. Game 5 is Monday in Dallas.

“It means a lot,” Landeskog told reporters after the win. “Obviously, I’ve envisioned scoring again for a long time. There obviously days when I didn’t know if I was ever going to score again. It obviously feels good. It’s a tight playoff series in a big game here at home. To get to do it here at home in front of our fans obviously means a means a lot. Super exciting. Hopefully more to come.”

A short-handed goal from Logan O’Connor midway through the first period followed by a late power-play goal from Nathan MacKinnon staked the Avalanche to a 2-0 lead entering the second period.

That set the stage for Landeskog, who was in the slot when Brock Nelson fed a pass that the 32-year-old winger launched for a one-timer that beat Stars goaltender Jake Oettinger for a 3-0 lead.

Landeskog, who was playing on the second line, was instantly mobbed by his teammates on the nice such as Samuel Girard, Valeri Nichushkin, Devon Toews and Nelson, who joined the Avalanche at the NHL trade deadline.

As Landeskog returned to the bench, he was congratulated by the entire team which also included a hug from a smiling MacKinnon, who along with Landeskog, have been with the franchise for more than a decade.

“I was just proud of him again,” Avalanche coach Jared Bednar told reporters after the game. “I was proud of him regardless of if he scores or not because I know what he’s gone through, and I know how difficult that was. I think that takes it to another level. You know he wants to come back and contribute like he did in the past and he’s off to a great start.”

Landeskog’s goal was the latest milestone in what’s been a lengthy recovery from a chronically injured right knee. He missed what amounted to 1,032 days since his last NHL game.

In that time, the Avalanche have remained in a championship window but have dramatically altered their roster. The Avs have nine players from that championship team who have remained with the franchise and have since reshuffled a roster that led to them re-acquiring defenseman Erik Johnson, one of Landeskog’s closest friends, in their bid for the fourth title in franchise history.

Even with all the changes, there were still questions about when they could see Landeskog return to the lineup. And if Landeskog did return, what he could look like?

His first professional game in three years came April 11 with the Avalanche’s AHL affiliate where he logged 15 minutes. Landeskog would then score a goal and get an assist in his second and final game.

And much like his AHL stint, all it took was two games for Landeskog to score and have another two-point performance.

While Landeskog’s goal became the most celebrated moment of the evening, what he did to help create the Avalanche’s fourth goal was an example of why he’s so crucial to their title aspirations.

Landeskog played a pass to Nelson who then found a Girard for a shot from the point that gave the Avs a 4-0 lead in the fourth. In the time Landeskog passed the puck, he anchored himself at the net front to gain position on 6-foot-7 Stars defensemen Lian Bichsel to screen goaltender Casey DeSmith, who replaced Oettinger for the third period.

Jockeying with Bichsel, who is six inches taller and 16 pounds heavier, allowed Landeskog to test both his strength and that right knee to gain leverage.

The result? Girard’s shot found space in traffic with Landeskog making it hard for DeSmith to see the puck.

“He’s a big boy,” Landeskog said with a smile. “He’s a big strong guy, a physical player and hard to play against. I was trying to get in front of their goal, and he was trying to get me out of there. It was a good battle.”

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Several killed after vehicle drives into crowd at street festival, police in Vancouver say

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Several killed after vehicle drives into crowd at street festival, police in Vancouver say

A number of people have been killed and multiple others injured after a driver drove into a crowd at a street festival in Vancouver, police have said.

The driver has been taken into custody after the incident shortly after 8pm local time on Saturday, police added.

People were in the area near 41st Avenue and Fraser Street for the Lapu Lapu Day Block Party, named after a national hero of the Philippines.

Vancouver’s mayor Ken Sim said in a post on X: “I am shocked and deeply saddened by the horrific incident at today’s Lapu Lapu Day event.”

He added: “Our thoughts are with all those affected and with Vancouver’s Filipino community during this incredibly difficult time.”

Video posted on social media showed victims and debris strewn across a long stretch of road, with at least seven people lying immobile on the ground.

A black SUV with a crumpled front section could be seen in photos from the scene.

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